rs143140501

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_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:3

Conservation

PhyloP100: 0.112

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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 male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC6	NM_001127198.5 linkuse as main transcript	c.2021+11C>T		intron_variant		ENST00000590602.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC6	ENST00000590602.6 linkuse as main transcript	c.2021+11C>T		intron_variant		2	NM_001127198.5	P1	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

GnomAD3 exomes

AF:

0.0228

AC:

5227

AN:

229718

Hom.:

AF XY:

0.0233

AC XY:

2909

AN XY:

124858

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 SAS exome

AF:

0.0104

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

Gnomad4 AFR exome

AF:

0.0126

Gnomad4 AMR exome

AF:

0.0181

Gnomad4 ASJ exome

AF:

0.0233

Gnomad4 EAS exome

AF:

0.0000510

Gnomad4 SAS exome

AF:

0.0109

Gnomad4 FIN exome

AF:

0.0284

Gnomad4 NFE exome

AF:

0.0318

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.0246

AC:

3739

AN:

151906

Hom.:

Cov.:

AF XY:

0.0244

AC XY:

1815

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0135

Gnomad4 AMR

AF:

0.0315

Gnomad4 ASJ

AF:

0.0214

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00788

Gnomad4 FIN

AF:

0.0272

Gnomad4 NFE

AF:

0.0325

Gnomad4 OTH

AF:

0.0299

Alfa

AF:

0.0273

Hom.:

Bravo

AF:

0.0249

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

Epidermodysplasia verruciformis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

Cadd

Benign

2.7

Dann

Benign

0.91

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over