Variant 17-78139331-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.1902+91G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,459,682 control chromosomes in the GnomAD database, including 150,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14788 hom., cov: 32)

Exomes 𝑓: 0.45 ( 135368 hom. )

Consequence

TMC8
NM_152468.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.47

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 (BayesDel_noAF=-0.86).

BP6

Variant 17-78139331-G-T is Benign according to our data. Variant chr17-78139331-G-T is described in ClinVar as [Benign]. Clinvar id is 1250684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 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.1902+91G>T		intron_variant		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.1902+91G>T		intron_variant		1	NM_152468.5	ENSP00000325561.4		Q8IU68-1

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

65946

AN:

151874

Hom.:

14782

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.548

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.485

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.455

GnomAD4 exome

AF:

0.451

AC:

589602

AN:

1307690

Hom.:

135368

AF XY:

0.452

AC XY:

295358

AN XY:

653892

show subpopulations

Gnomad4 AFR exome

AF:

0.400

Gnomad4 AMR exome

AF:

0.276

Gnomad4 ASJ exome

AF:

0.552

Gnomad4 EAS exome

AF:

0.228

Gnomad4 SAS exome

AF:

0.405

Gnomad4 FIN exome

AF:

0.478

Gnomad4 NFE exome

AF:

0.468

Gnomad4 OTH exome

AF:

0.453

GnomAD4 genome

AF:

0.434

AC:

65990

AN:

151992

Hom.:

14788

Cov.:

AF XY:

0.430

AC XY:

31964

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.398

Gnomad4 AMR

AF:

0.363

Gnomad4 ASJ

AF:

0.548

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.394

Gnomad4 FIN

AF:

0.485

Gnomad4 NFE

AF:

0.474

Gnomad4 OTH

AF:

0.457

Alfa

AF:

0.472

Hom.:

22718

Bravo

AF:

0.425

Asia WGS

AF:

0.331

AC:

1153

AN:

3478

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	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 50% of patients studied by a panel of primary immunodeficiencies. Number of patients: 44. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

9.4

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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