Variant rs141186150 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_152468.5(TMC8):c.1725C>T(p.Val575=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,613,978 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 4 hom. )

Consequence

TMC8
NM_152468.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.392

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 17-78138634-C-T is Benign according to our data. Variant chr17-78138634-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 456025.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78138634-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.392 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00117 (179/152394) while in subpopulation NFE AF= 0.00187 (127/68034). AF 95% confidence interval is 0.0016. There are 2 homozygotes in gnomad4. There are 76 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMC8	NM_152468.5 linkuse as main transcript	c.1725C>T	p.Val575=	synonymous_variant	14/16	ENST00000318430.10	NP_689681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMC8	ENST00000318430.10 linkuse as main transcript	c.1725C>T	p.Val575=	synonymous_variant	14/16	1	NM_152468.5	ENSP00000325561	P2	Q8IU68-1

Frequencies

GnomAD3 genomes

AF:

0.00119

AC:

181

AN:

152276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00125

AC:

315

AN:

251046

Hom.:

AF XY:

0.00122

AC XY:

165

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.000994

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.00153

AC:

2231

AN:

1461584

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

1120

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00137

Gnomad4 FIN exome

AF:

0.00141

Gnomad4 NFE exome

AF:

0.00171

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00117

AC:

179

AN:

152394

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74526

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000979

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00187

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.000997

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00142

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epidermodysplasia verruciformis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

3.4

DANN

Benign

0.77

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