Variant 17-78134866-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.988-4G>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 0.0756 in 1,613,664 control chromosomes in the GnomAD database, including 5,020 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 553 hom., cov: 32)

Exomes 𝑓: 0.075 ( 4467 hom. )

Consequence

TMC8
NM_152468.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003550

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.18

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=-0.86).

BP6

Variant 17-78134866-G-T is Benign according to our data. Variant chr17-78134866-G-T is described in ClinVar as [Benign]. Clinvar id is 1098860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-78134866-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0854 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.988-4G>T		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.988-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_152468.5	ENSP00000325561	P2	Q8IU68-1

Frequencies

GnomAD3 genomes

AF:

0.0837

AC:

12722

AN:

152044

Hom.:

553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0878

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.0634

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.0909

Gnomad SAS

AF:

0.0667

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0790

Gnomad OTH

AF:

0.0987

GnomAD3 exomes

AF:

0.0785

AC:

19674

AN:

250726

Hom.:

872

AF XY:

0.0796

AC XY:

10807

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.0880

Gnomad AMR exome

AF:

0.0472

Gnomad ASJ exome

AF:

0.143

Gnomad EAS exome

AF:

0.0960

Gnomad SAS exome

AF:

0.0589

Gnomad FIN exome

AF:

0.0896

Gnomad NFE exome

AF:

0.0807

Gnomad OTH exome

AF:

0.0882

GnomAD4 exome

AF:

0.0747

AC:

109225

AN:

1461502

Hom.:

4467

Cov.:

AF XY:

0.0754

AC XY:

54854

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.0916

Gnomad4 AMR exome

AF:

0.0497

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.0829

Gnomad4 SAS exome

AF:

0.0623

Gnomad4 FIN exome

AF:

0.0911

Gnomad4 NFE exome

AF:

0.0729

Gnomad4 OTH exome

AF:

0.0809

GnomAD4 genome

AF:

0.0837

AC:

12736

AN:

152162

Hom.:

553

Cov.:

AF XY:

0.0841

AC XY:

6258

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0878

Gnomad4 AMR

AF:

0.0632

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.0907

Gnomad4 SAS

AF:

0.0667

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.0790

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0666

Hom.:

167

Bravo

AF:

0.0829

Asia WGS

AF:

0.0780

AC:

269

AN:

3478

EpiCase

AF:

0.0920

EpiControl

AF:

0.0872

ClinVar

Significance: Benign

Submissions summary: Benign:4

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, susceptibility to, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

May 18, 2021

- -

Epidermodysplasia verruciformis

Benign:1

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

-0.86

CADD

Benign

0.28

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: 28

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