dbSNP rs9807014: TMC6:c.*592G>A (chr17-78112556-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.61

Publications

8 publications found

Variant links:

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

TMC6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC6	NM_001127198.5 link	c.*592G>A		3_prime_UTR_variant	Exon 20 of 20	ENST00000590602.6	NP_001120670.1	Q7Z403-1A0A024R8V2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC6	ENST00000590602.6 link	c.*592G>A		3_prime_UTR_variant	Exon 20 of 20	2	NM_001127198.5	ENSP00000465261.1		Q7Z403-1

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23605

AN:

152196

Hom.:

2112

Cov.:

show subpopulations

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.:

AF XY:

0.172

AC XY:

1022

AN XY:

5926

show subpopulations

African (AFR)

AF:

0.0781

AC:

AN:

American (AMR)

AF:

0.182

AC:

208

AN:

1142

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

AN:

174

East Asian (EAS)

AF:

0.244

AC:

AN:

180

South Asian (SAS)

AF:

0.190

AC:

449

AN:

2366

European-Finnish (FIN)

AF:

0.188

AC:

AN:

324

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.161

AC:

995

AN:

6174

Other (OTH)

AF:

0.174

AC:

102

AN:

586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

157

236

314

393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.155

AC:

23605

AN:

152316

Hom.:

2114

Cov.:

AF XY:

0.157

AC XY:

11720

AN XY:

74474

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

12071

AN:

68012

Other (OTH)

AF:

0.179

AC:

378

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1053

2106

3159

4212

5265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

(source)

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)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over