Variant chr17-78113277-G-A 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_001127198.5(TMC6):c.2355-66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,499,028 control chromosomes in the GnomAD database, including 22,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3819 hom., cov: 33)

Exomes 𝑓: 0.16 ( 19177 hom. )

Consequence

TMC6
NM_001127198.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.266

Variant links:

Genes affected

TMC6 (HGNC:18021): (transmembrane channel like 6) 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 10 transmembrane domains and 2 leucine zipper motifs. [provided by RefSeq, Jul 2008]

TMC6 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=-0.91).

BP6

Variant 17-78113277-G-A is Benign according to our data. Variant chr17-78113277-G-A is described in ClinVar as [Benign]. Clinvar id is 1279056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC6	NM_001127198.5 linkuse as main transcript	c.2355-66C>T		intron_variant		ENST00000590602.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC6	ENST00000590602.6 linkuse as main transcript	c.2355-66C>T		intron_variant		2	NM_001127198.5	P1	Q7Z403-1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31447

AN:

152092

Hom.:

3809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.196

GnomAD4 exome

AF:

0.160

AC:

216109

AN:

1346818

Hom.:

19177

AF XY:

0.164

AC XY:

108438

AN XY:

662570

show subpopulations

Gnomad4 AFR exome

AF:

0.333

Gnomad4 AMR exome

AF:

0.216

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.257

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.106

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.207

AC:

31502

AN:

152210

Hom.:

3819

Cov.:

AF XY:

0.208

AC XY:

15476

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.327

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.157

Gnomad4 EAS

AF:

0.258

Gnomad4 SAS

AF:

0.304

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.201

Alfa

AF:

0.143

Hom.:

893

Bravo

AF:

0.220

Asia WGS

AF:

0.304

AC:

1053

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 42% of patients studied by a panel of primary immunodeficiencies. Number of patients: 37. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

5.1

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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