Variant rs16970849 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.1349+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 1,612,106 control chromosomes in the GnomAD database, including 7,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1506 hom., cov: 33)

Exomes 𝑓: 0.061 ( 5912 hom. )

Consequence

TMC8
NM_152468.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.98

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=-0.81).

BP6

Variant 17-78137827-G-A is Benign according to our data. Variant chr17-78137827-G-A is described in ClinVar as [Benign]. Clinvar id is 1167028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-78137827-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.219 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.1349+13G>A		intron_variant		ENST00000318430.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC8	ENST00000318430.10 linkuse as main transcript	c.1349+13G>A		intron_variant		1	NM_152468.5	P2	Q8IU68-1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17211

AN:

152166

Hom.:

1494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.0559

Gnomad FIN

AF:

0.0906

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0450

Gnomad OTH

AF:

0.0965

GnomAD3 exomes

AF:

0.114

AC:

28334

AN:

248864

Hom.:

3282

AF XY:

0.0983

AC XY:

13271

AN XY:

135068

show subpopulations

Gnomad AFR exome

AF:

0.205

Gnomad AMR exome

AF:

0.350

Gnomad ASJ exome

AF:

0.0489

Gnomad EAS exome

AF:

0.194

Gnomad SAS exome

AF:

0.0486

Gnomad FIN exome

AF:

0.0849

Gnomad NFE exome

AF:

0.0454

Gnomad OTH exome

AF:

0.0889

GnomAD4 exome

AF:

0.0613

AC:

89483

AN:

1459822

Hom.:

5912

Cov.:

AF XY:

0.0593

AC XY:

43041

AN XY:

726256

show subpopulations

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.335

Gnomad4 ASJ exome

AF:

0.0497

Gnomad4 EAS exome

AF:

0.214

Gnomad4 SAS exome

AF:

0.0509

Gnomad4 FIN exome

AF:

0.0841

Gnomad4 NFE exome

AF:

0.0402

Gnomad4 OTH exome

AF:

0.0689

GnomAD4 genome

AF:

0.113

AC:

17267

AN:

152284

Hom.:

1506

Cov.:

AF XY:

0.118

AC XY:

8792

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.0493

Gnomad4 EAS

AF:

0.195

Gnomad4 SAS

AF:

0.0557

Gnomad4 FIN

AF:

0.0906

Gnomad4 NFE

AF:

0.0450

Gnomad4 OTH

AF:

0.0978

Alfa

AF:

0.0530

Hom.:

Bravo

AF:

0.130

Asia WGS

AF:

0.133

AC:

463

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 38. Only high quality variants are reported. -

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

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

Cadd

Benign

Dann

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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