17-78117873-G-C

Variant names:

• chr17-78117873-G-C
• rs2613516
• NM_001127198.5:c.1950C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001127198.5(TMC6):​c.1950C>G​(p.Thr650Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,606,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T650T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMC6 NM_001127198.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0930
• Publications: 10 publications found

Genes affected

TMC6 (HGNC:18021): (transmembrane channel like 6) Epidermodysplasia verruciformis (EV) is an autosomal recessive dermatosis characterized by abnormal susceptibility to human papillomaviruses (HPVs) and a high rate of progression to squamous cell carcinoma on sun-exposed skin. EV is caused by mutations in either of two adjacent genes located on chromosome 17q25.3. Both of these genes encode integral membrane proteins that localize to the endoplasmic reticulum and are predicted to form transmembrane channels. This gene encodes a transmembrane channel-like protein with 10 transmembrane domains and 2 leucine zipper motifs. [provided by RefSeq, Jul 2008]

TMC6 Gene-Disease associations (from GenCC):

• epidermodysplasia verruciformis, susceptibility to, 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• epidermodysplasia verruciformis

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-78117873-G-C is Benign according to our data. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78117873-G-C is described in CliVar as Likely_benign. Clinvar id is 2126065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.093 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC6	NM_001127198.5	c.1950C>G	p.Thr650Thr	synonymous_variant	Exon 16 of 20	ENST00000590602.6	NP_001120670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC6	ENST00000590602.6	c.1950C>G	p.Thr650Thr	synonymous_variant	Exon 16 of 20	2	NM_001127198.5	ENSP00000465261.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000856 AC: 2 AN: 233626 AF XY: 0.00000787

Gnomad AFR exome AF: 0.0000688

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454250 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 722794

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 43700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25910

East Asian (EAS) AF: 0.00 AC: 0 AN: 39456

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108880

Other (OTH) AF: 0.00 AC: 0 AN: 60080

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74308

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 1279

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epidermodysplasia verruciformis Benign:1

Oct 25, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.0
DANN	Benign	0.67
PhyloP100		0.093

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2613516; hg19: chr17-76113954;