rs143140501

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001127198.5(TMC6):c.2021+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,602,370 control chromosomes in the GnomAD database, including 695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 58 hom., cov: 33)

Exomes 𝑓: 0.028 ( 637 hom. )

Consequence

TMC6
NM_001127198.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.112

Publications

0 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 -16 ACMG points.

BP6

Variant 17-78117791-G-A is Benign according to our data. Variant chr17-78117791-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 403544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0246 (3739/151906) while in subpopulation NFE AF = 0.0325 (2210/67926). AF 95% confidence interval is 0.0314. There are 58 homozygotes in GnomAd4. There are 1815 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC6	NM_001127198.5 link	c.2021+11C>T		intron_variant	Intron 16 of 19	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.2021+11C>T		intron_variant	Intron 16 of 19	2	NM_001127198.5	ENSP00000465261.1		Q7Z403-1

Frequencies

GnomAD3 genomes

AF:

0.0247

AC:

3744

AN:

151786

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0135

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0316

Gnomad ASJ

AF:

0.0214

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00829

Gnomad FIN

AF:

0.0272

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0325

Gnomad OTH

AF:

0.0307

GnomAD2 exomes

AF:

0.0228

AC:

5227

AN:

229718

AF XY:

0.0233

show subpopulations

Gnomad AFR exome

AF:

0.0114

Gnomad AMR exome

AF:

0.0177

Gnomad ASJ exome

AF:

0.0253

Gnomad EAS exome

AF:

0.000173

Gnomad FIN exome

AF:

0.0282

Gnomad NFE exome

AF:

0.0318

Gnomad OTH exome

AF:

0.0263

GnomAD4 exome

AF:

0.0284

AC:

41172

AN:

1450464

Hom.:

637

Cov.:

AF XY:

0.0280

AC XY:

20171

AN XY:

720608

show subpopulations

African (AFR)

AF:

0.0126

AC:

417

AN:

33212

American (AMR)

AF:

0.0181

AC:

790

AN:

43718

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

602

AN:

25862

East Asian (EAS)

AF:

0.0000510

AC:

AN:

39198

South Asian (SAS)

AF:

0.0109

AC:

920

AN:

84686

European-Finnish (FIN)

AF:

0.0284

AC:

1456

AN:

51332

Middle Eastern (MID)

AF:

0.0391

AC:

224

AN:

5722

European-Non Finnish (NFE)

AF:

0.0318

AC:

35179

AN:

1106812

Other (OTH)

AF:

0.0264

AC:

1582

AN:

59922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

2849

5698

8548

11397

14246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0246

AC:

3739

AN:

151906

Hom.:

Cov.:

AF XY:

0.0244

AC XY:

1815

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.0135

AC:

558

AN:

41392

American (AMR)

AF:

0.0315

AC:

482

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0214

AC:

AN:

3466

East Asian (EAS)

AF:

0.000194

AC:

AN:

5160

South Asian (SAS)

AF:

0.00788

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0272

AC:

287

AN:

10550

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0325

AC:

2210

AN:

67926

Other (OTH)

AF:

0.0299

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

179

358

536

715

894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0287

Hom.:

Bravo

AF:

0.0249

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 10, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Epidermodysplasia verruciformis

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: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

-0.76

CADD

Benign

2.7

(source)

DANN

Benign

0.91

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.50

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.50

Position offset: 2

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

Publications

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rs143140501

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over