Variant rs11651675 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152468.5(TMC8):c.1501G>A(p.Val501Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 1,613,810 control chromosomes in the GnomAD database, including 1,473 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 110 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1363 hom. )

Consequence

TMC8
NM_152468.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.59

Variant links:

Genes affected

TMC8 (HGNC:20474): (transmembrane channel like 8) 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 8 predicted transmembrane domains and 3 leucine zipper motifs. [provided by RefSeq, Jul 2008]

TMC8 links:

TMC8 (HGNC:):

TMC8 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 (MetaRNN=0.0021557808).

BP6

Variant 17-78138156-G-A is Benign according to our data. Variant chr17-78138156-G-A is described in ClinVar as [Benign]. Clinvar id is 456022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-78138156-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMC8	NM_152468.5 linkuse as main transcript	c.1501G>A	p.Val501Ile	missense_variant	12/16	ENST00000318430.10	NP_689681.2	Q8IU68-1A0A024R8N8B3KXZ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMC8	ENST00000318430.10 linkuse as main transcript	c.1501G>A	p.Val501Ile	missense_variant	12/16	1	NM_152468.5	ENSP00000325561.4		Q8IU68-1

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

5027

AN:

151972

Hom.:

111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0232

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0335

Gnomad ASJ

AF:

0.0444

Gnomad EAS

AF:

0.00810

Gnomad SAS

AF:

0.0966

Gnomad FIN

AF:

0.0205

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0376

Gnomad OTH

AF:

0.0399

GnomAD3 exomes

AF:

0.0378

AC:

9488

AN:

250886

Hom.:

275

AF XY:

0.0411

AC XY:

5582

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0234

Gnomad AMR exome

AF:

0.0256

Gnomad ASJ exome

AF:

0.0400

Gnomad EAS exome

AF:

0.00935

Gnomad SAS exome

AF:

0.0873

Gnomad FIN exome

AF:

0.0203

Gnomad NFE exome

AF:

0.0379

Gnomad OTH exome

AF:

0.0404

GnomAD4 exome

AF:

0.0393

AC:

57411

AN:

1461720

Hom.:

1363

Cov.:

AF XY:

0.0408

AC XY:

29697

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0228

Gnomad4 AMR exome

AF:

0.0249

Gnomad4 ASJ exome

AF:

0.0391

Gnomad4 EAS exome

AF:

0.00370

Gnomad4 SAS exome

AF:

0.0843

Gnomad4 FIN exome

AF:

0.0214

Gnomad4 NFE exome

AF:

0.0386

Gnomad4 OTH exome

AF:

0.0444

GnomAD4 genome

AF:

0.0331

AC:

5033

AN:

152090

Hom.:

110

Cov.:

AF XY:

0.0334

AC XY:

2480

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0231

Gnomad4 AMR

AF:

0.0335

Gnomad4 ASJ

AF:

0.0444

Gnomad4 EAS

AF:

0.00812

Gnomad4 SAS

AF:

0.0967

Gnomad4 FIN

AF:

0.0205

Gnomad4 NFE

AF:

0.0376

Gnomad4 OTH

AF:

0.0413

Alfa

AF:

0.0361

Hom.:

237

Bravo

AF:

0.0315

TwinsUK

AF:

0.0307

AC:

114

ALSPAC

AF:

0.0415

AC:

160

ESP6500AA

AF:

0.0222

AC:

ESP6500EA

AF:

0.0386

AC:

332

ExAC

AF:

0.0382

AC:

4644

Asia WGS

AF:

0.0590

AC:

203

AN:

3478

EpiCase

AF:

0.0412

EpiControl

AF:

0.0434

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	- -

Epidermodysplasia verruciformis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0080

DANN

Benign

0.87

DEOGEN2

Benign

0.0032

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.50

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.44

N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

0.17

N;.

REVEL

Benign

0.043

Sift

Benign

0.54

T;.

Sift4G

Benign

0.58

T;T

Polyphen

0.0040

B;.

Vest4

0.033

MPC

0.13

ClinPred

0.0022

GERP RS

-6.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.026

gMVP

0.063

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

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