Variant chr17-78121719-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001127198.5(TMC6):c.1228-8G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00878 in 1,574,284 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0087 ( 63 hom. )

Consequence

TMC6
NM_001127198.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001120

Clinical Significance

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

Conservation

PhyloP100: -2.64

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-78121719-C-T is Benign according to our data. Variant chr17-78121719-C-T is described in ClinVar as [Benign]. Clinvar id is 456005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00956 (1456/152300) while in subpopulation AFR AF= 0.0121 (501/41558). AF 95% confidence interval is 0.0112. There are 5 homozygotes in gnomad4. There are 696 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMC6	NM_001127198.5 linkuse as main transcript	c.1228-8G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		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.1228-8G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_001127198.5	ENSP00000465261	P1	Q7Z403-1

Frequencies

GnomAD3 genomes

AF:

0.00957

AC:

1456

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0190

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00979

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00753

AC:

1401

AN:

186126

Hom.:

AF XY:

0.00697

AC XY:

713

AN XY:

102352

show subpopulations

Gnomad AFR exome

AF:

0.0132

Gnomad AMR exome

AF:

0.00309

Gnomad ASJ exome

AF:

0.00387

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000896

Gnomad FIN exome

AF:

0.0175

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.00772

GnomAD4 exome

AF:

0.00870

AC:

12371

AN:

1421984

Hom.:

Cov.:

AF XY:

0.00830

AC XY:

5849

AN XY:

704708

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.00340

Gnomad4 ASJ exome

AF:

0.00499

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000756

Gnomad4 FIN exome

AF:

0.0167

Gnomad4 NFE exome

AF:

0.00952

Gnomad4 OTH exome

AF:

0.00825

GnomAD4 genome

AF:

0.00956

AC:

1456

AN:

152300

Hom.:

Cov.:

AF XY:

0.00935

AC XY:

696

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0121

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0190

Gnomad4 NFE

AF:

0.00979

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00893

Hom.:

Bravo

AF:

0.00878

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Epidermodysplasia verruciformis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.60

DANN

Benign

0.78

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.026

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