Variant 17-78138569-G-T 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.1665-5G>T 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 0.0386 in 1,613,736 control chromosomes in the GnomAD database, including 1,466 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 0.033 ( 109 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1357 hom. )

Consequence

TMC8
NM_152468.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001925

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.385

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 17-78138569-G-T is Benign according to our data. Variant chr17-78138569-G-T is described in ClinVar as [Benign]. Clinvar id is 456024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-78138569-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC8	NM_152468.5 linkuse as main transcript	c.1665-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000318430.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC8	ENST00000318430.10 linkuse as main transcript	c.1665-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_152468.5	P2	Q8IU68-1

Frequencies

GnomAD3 genomes

AF:

0.0327

AC:

4979

AN:

152174

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0300

Gnomad ASJ

AF:

0.0444

Gnomad EAS

AF:

0.00808

Gnomad SAS

AF:

0.0978

Gnomad FIN

AF:

0.0209

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0376

Gnomad OTH

AF:

0.0382

GnomAD3 exomes

AF:

0.0376

AC:

9428

AN:

250772

Hom.:

273

AF XY:

0.0409

AC XY:

5543

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.0233

Gnomad AMR exome

AF:

0.0250

Gnomad ASJ exome

AF:

0.0400

Gnomad EAS exome

AF:

0.00931

Gnomad SAS exome

AF:

0.0872

Gnomad FIN exome

AF:

0.0203

Gnomad NFE exome

AF:

0.0376

Gnomad OTH exome

AF:

0.0402

GnomAD4 exome

AF:

0.0392

AC:

57233

AN:

1461444

Hom.:

1357

Cov.:

AF XY:

0.0407

AC XY:

29606

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.0223

Gnomad4 AMR exome

AF:

0.0243

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:

0.0385

Gnomad4 OTH exome

AF:

0.0443

GnomAD4 genome

AF:

0.0327

AC:

4985

AN:

152292

Hom.:

109

Cov.:

AF XY:

0.0330

AC XY:

2454

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0229

Gnomad4 AMR

AF:

0.0300

Gnomad4 ASJ

AF:

0.0444

Gnomad4 EAS

AF:

0.00810

Gnomad4 SAS

AF:

0.0978

Gnomad4 FIN

AF:

0.0209

Gnomad4 NFE

AF:

0.0376

Gnomad4 OTH

AF:

0.0397

Alfa

AF:

0.0271

Hom.:

Bravo

AF:

0.0312

Asia WGS

AF:

0.0590

AC:

204

AN:

3478

EpiCase

AF:

0.0411

EpiControl

AF:

0.0433

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Epidermodysplasia verruciformis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

Cadd

Benign

2.7

Dann

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0

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