chr17-78112992-C-T

Position:

• chr17-78112992-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001127198.5(TMC6):​c.*156G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 797,506 control chromosomes in the GnomAD database, including 2,577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (401 hom., cov: 33)
  • Exomes 𝑓: 0.075 (2176 hom.)
• Consequence: TMC6 NM_001127198.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.144

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-78112992-C-T is Benign according to our data. Variant chr17-78112992-C-T is described in ClinVar as [Benign]. Clinvar id is 1286448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMC6	NM_001127198.5	c.*156G>A		3_prime_UTR_variant	20/20	ENST00000590602.6	NP_001120670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMC6	ENST00000590602	c.*156G>A		3_prime_UTR_variant	20/20	2	NM_001127198.5	ENSP00000465261.1

Frequencies

GnomAD3 genomes AF: 0.0659 AC: 10035 AN: 152228 Hom.: 400 Cov.: 33

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0538

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0721

Gnomad OTH AF: 0.0599

GnomAD4 exome AF: 0.0752 AC: 48514 AN: 645160 Hom.: 2176 Cov.: 8 AF XY: 0.0783 AC XY: 26478 AN XY: 338024

Gnomad4 AFR exome AF: 0.0546

Gnomad4 AMR exome AF: 0.0404

Gnomad4 ASJ exome AF: 0.0392

Gnomad4 EAS exome AF: 0.146

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0277

Gnomad4 NFE exome AF: 0.0704

Gnomad4 OTH exome AF: 0.0762

GnomAD4 genome AF: 0.0659 AC: 10033 AN: 152346 Hom.: 401 Cov.: 33 AF XY: 0.0662 AC XY: 4933 AN XY: 74496

Gnomad4 AFR AF: 0.0564

Gnomad4 AMR AF: 0.0538

Gnomad4 ASJ AF: 0.0397

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.0721

Gnomad4 OTH AF: 0.0583

Alfa AF: 0.0627 Hom.: 342

Bravo AF: 0.0653

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.7
DANN	Benign	0.78
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs2253277; hg19: chr17-76109073;