Variant 17-78125841-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001127198.5(TMC6):c.315G>A(p.Thr105Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,552,718 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 4 hom. )

Consequence

TMC6
NM_001127198.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.79

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:

TMC6 (HGNC:):

TMC6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 17-78125841-C-T is Benign according to our data. Variant chr17-78125841-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 456015.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-78125841-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0012 (183/152306) while in subpopulation NFE AF= 0.00212 (144/68014). AF 95% confidence interval is 0.00184. There are 0 homozygotes in gnomad4. There are 80 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMC6	NM_001127198.5 linkuse as main transcript	c.315G>A	p.Thr105Thr	synonymous_variant	5/20	ENST00000590602.6	NP_001120670.1	Q7Z403-1A0A024R8V2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMC6	ENST00000590602.6 linkuse as main transcript	c.315G>A	p.Thr105Thr	synonymous_variant	5/20	2	NM_001127198.5	ENSP00000465261.1		Q7Z403-1

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

183

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00212

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000955

AC:

151

AN:

158150

Hom.:

AF XY:

0.000910

AC XY:

AN XY:

83558

show subpopulations

Gnomad AFR exome

AF:

0.000793

Gnomad AMR exome

AF:

0.000200

Gnomad ASJ exome

AF:

0.000235

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000873

Gnomad FIN exome

AF:

0.000259

Gnomad NFE exome

AF:

0.00211

Gnomad OTH exome

AF:

0.000225

GnomAD4 exome

AF:

0.00198

AC:

2772

AN:

1400412

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

1367

AN XY:

691042

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.000139

Gnomad4 ASJ exome

AF:

0.000238

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000504

Gnomad4 FIN exome

AF:

0.000247

Gnomad4 NFE exome

AF:

0.00240

Gnomad4 OTH exome

AF:

0.00188

GnomAD4 genome

AF:

0.00120

AC:

183

AN:

152306

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00212

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.00117

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epidermodysplasia verruciformis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.1

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: -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