rs2613516

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001127198.5(TMC6):c.1950C>T(p.Thr650=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,606,306 control chromosomes in the GnomAD database, including 18,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1295 hom., cov: 33)

Exomes 𝑓: 0.15 ( 17575 hom. )

Consequence

TMC6
NM_001127198.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.0930

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 17-78117873-G-A is Benign according to our data. Variant chr17-78117873-G-A is described in ClinVar as [Benign]. Clinvar id is 1165515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-78117873-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.093 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMC6	NM_001127198.5 linkuse as main transcript	c.1950C>T	p.Thr650=	synonymous_variant	16/20	ENST00000590602.6	NP_001120670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMC6	ENST00000590602.6 linkuse as main transcript	c.1950C>T	p.Thr650=	synonymous_variant	16/20	2	NM_001127198.5	ENSP00000465261	P1	Q7Z403-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17595

AN:

152106

Hom.:

1295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0281

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.138

AC:

32183

AN:

233626

Hom.:

2304

AF XY:

0.143

AC XY:

18189

AN XY:

127110

show subpopulations

Gnomad AFR exome

AF:

0.0236

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.134

Gnomad SAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.153

AC:

222358

AN:

1454080

Hom.:

17575

Cov.:

AF XY:

0.153

AC XY:

110852

AN XY:

722692

show subpopulations

Gnomad4 AFR exome

AF:

0.0247

Gnomad4 AMR exome

AF:

0.103

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.136

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.158

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.116

AC:

17583

AN:

152226

Hom.:

1295

Cov.:

AF XY:

0.116

AC XY:

8619

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0280

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.148

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.146

Gnomad4 NFE

AF:

0.153

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.132

Hom.:

973

Bravo

AF:

0.110

Asia WGS

AF:

0.130

AC:

452

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

Epidermodysplasia verruciformis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

7.1

DANN

Benign

0.82

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