rs9807014

Variant names:

• chr17-78112556-C-T
• rs9807014
• NM_001127198.5:c.*592G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127198.5(TMC6):​c.*592G>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 0.156 in 163,356 control chromosomes in the GnomAD database, including 2,295 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2114 hom., cov: 33)
  • Exomes 𝑓: 0.17 (181 hom.)
• Consequence: TMC6 NM_001127198.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 8 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: Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• epidermodysplasia verruciformis

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127198.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC6	NM_001127198.5	MANE Select	c.*592G>A		3_prime_UTR	Exon 20 of 20	NP_001120670.1	Q7Z403-1
	TMC6	NM_001374596.1		c.*592G>A		3_prime_UTR	Exon 20 of 20	NP_001361525.1	Q7Z403-1
	TMC6	NM_001374593.1		c.*592G>A		3_prime_UTR	Exon 19 of 19	NP_001361522.1	A0A8V8TLY1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC6	ENST00000590602.6	TSL:2 MANE Select	c.*592G>A		3_prime_UTR	Exon 20 of 20	ENSP00000465261.1	Q7Z403-1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23605 AN: 152196 Hom.: 2112 Cov.: 33

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.173 AC: 1909 AN: 11040 Hom.: 181 Cov.: 0 AF XY: 0.172 AC XY: 1022 AN XY: 5926

African (AFR) AF: 0.0781 AC: 5 AN: 64

American (AMR) AF: 0.182 AC: 208 AN: 1142

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 40 AN: 174

East Asian (EAS) AF: 0.244 AC: 44 AN: 180

South Asian (SAS) AF: 0.190 AC: 449 AN: 2366

European-Finnish (FIN) AF: 0.188 AC: 61 AN: 324

Middle Eastern (MID) AF: 0.167 AC: 5 AN: 30

European-Non Finnish (NFE) AF: 0.161 AC: 995 AN: 6174

Other (OTH) AF: 0.174 AC: 102 AN: 586

GnomAD4 genome AF: 0.155 AC: 23605 AN: 152316 Hom.: 2114 Cov.: 33 AF XY: 0.157 AC XY: 11720 AN XY: 74474

African (AFR) AF: 0.0735 AC: 3056 AN: 41584

American (AMR) AF: 0.176 AC: 2686 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3472

East Asian (EAS) AF: 0.225 AC: 1168 AN: 5182

South Asian (SAS) AF: 0.186 AC: 898 AN: 4832

European-Finnish (FIN) AF: 0.206 AC: 2183 AN: 10608

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12071 AN: 68012

Other (OTH) AF: 0.179 AC: 378 AN: 2116

Alfa AF: 0.174 Hom.: 4380

Bravo AF: 0.152

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.69
PhyloP100		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9807014; hg19: chr17-76108637;