Variant chr17-78133849-G-C 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 ENST00000318430.10(TMC8):c.669-4G>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,613,042 control chromosomes in the GnomAD database, including 1,050 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 79 hom., cov: 33)

Exomes 𝑓: 0.032 ( 971 hom. )

Consequence

TMC8
ENST00000318430.10 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003684

Clinical Significance

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

Conservation

PhyloP100: -0.0950

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:

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=-0.87).

BP6

Variant 17-78133849-G-C is Benign according to our data. Variant chr17-78133849-G-C is described in ClinVar as [Benign]. Clinvar id is 456027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-78133849-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0898 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.669-4G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		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.669-4G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_152468.5	ENSP00000325561	P2	Q8IU68-1

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3507

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00528

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.0307

Gnomad ASJ

AF:

0.0380

Gnomad EAS

AF:

0.00731

Gnomad SAS

AF:

0.0967

Gnomad FIN

AF:

0.0111

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0287

Gnomad OTH

AF:

0.0296

GnomAD3 exomes

AF:

0.0316

AC:

7859

AN:

248634

Hom.:

214

AF XY:

0.0354

AC XY:

4784

AN XY:

135310

show subpopulations

Gnomad AFR exome

AF:

0.00453

Gnomad AMR exome

AF:

0.0220

Gnomad ASJ exome

AF:

0.0355

Gnomad EAS exome

AF:

0.00708

Gnomad SAS exome

AF:

0.0883

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.0302

Gnomad OTH exome

AF:

0.0351

GnomAD4 exome

AF:

0.0315

AC:

46049

AN:

1460686

Hom.:

971

Cov.:

AF XY:

0.0335

AC XY:

24349

AN XY:

726614

show subpopulations

Gnomad4 AFR exome

AF:

0.00565

Gnomad4 AMR exome

AF:

0.0222

Gnomad4 ASJ exome

AF:

0.0345

Gnomad4 EAS exome

AF:

0.00317

Gnomad4 SAS exome

AF:

0.0865

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.0298

Gnomad4 OTH exome

AF:

0.0361

GnomAD4 genome

AF:

0.0230

AC:

3507

AN:

152356

Hom.:

Cov.:

AF XY:

0.0240

AC XY:

1789

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00529

Gnomad4 AMR

AF:

0.0307

Gnomad4 ASJ

AF:

0.0380

Gnomad4 EAS

AF:

0.00733

Gnomad4 SAS

AF:

0.0970

Gnomad4 FIN

AF:

0.0111

Gnomad4 NFE

AF:

0.0288

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0202

Hom.:

Bravo

AF:

0.0220

Asia WGS

AF:

0.0480

AC:

165

AN:

3478

EpiCase

AF:

0.0326

EpiControl

AF:

0.0359

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	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.4

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000037

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.040

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