rs143140501

Variant names:

• chr17-78117791-G-A
• rs143140501
• NM_001127198.5:c.2021+11C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-78117791-G-A
• chr17-78117791-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001127198.5(TMC6):​c.2021+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,602,370 control chromosomes in the GnomAD database, including 695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (58 hom., cov: 33)
  • Exomes 𝑓: 0.028 (637 hom.)
• Consequence: TMC6 NM_001127198.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.112

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 17-78117791-G-A is Benign according to our data. Variant chr17-78117791-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 403544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0246 (3739/151906) while in subpopulation NFE AF= 0.0325 (2210/67926). AF 95% confidence interval is 0.0314. There are 58 homozygotes in gnomad4. There are 1815 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC6	NM_001127198.5	c.2021+11C>T		intron_variant	Intron 16 of 19	ENST00000590602.6	NP_001120670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC6	ENST00000590602.6	c.2021+11C>T		intron_variant	Intron 16 of 19	2	NM_001127198.5	ENSP00000465261.1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3744 AN: 151786 Hom.: 58 Cov.: 33

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00829

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0307

GnomAD3 exomes AF: 0.0228 AC: 5227 AN: 229718 Hom.: 62 AF XY: 0.0233 AC XY: 2909 AN XY: 124858

Gnomad AFR exome AF: 0.0114

Gnomad AMR exome AF: 0.0177

Gnomad ASJ exome AF: 0.0253

Gnomad EAS exome AF: 0.000173

Gnomad SAS exome AF: 0.0104

Gnomad FIN exome AF: 0.0282

Gnomad NFE exome AF: 0.0318

Gnomad OTH exome AF: 0.0263

GnomAD4 exome AF: 0.0284 AC: 41172 AN: 1450464 Hom.: 637 Cov.: 32 AF XY: 0.0280 AC XY: 20171 AN XY: 720608

Gnomad4 AFR exome AF: 0.0126

Gnomad4 AMR exome AF: 0.0181

Gnomad4 ASJ exome AF: 0.0233

Gnomad4 EAS exome AF: 0.0000510

Gnomad4 SAS exome AF: 0.0109

Gnomad4 FIN exome AF: 0.0284

Gnomad4 NFE exome AF: 0.0318

Gnomad4 OTH exome AF: 0.0264

GnomAD4 genome AF: 0.0246 AC: 3739 AN: 151906 Hom.: 58 Cov.: 33 AF XY: 0.0244 AC XY: 1815 AN XY: 74254

Gnomad4 AFR AF: 0.0135

Gnomad4 AMR AF: 0.0315

Gnomad4 ASJ AF: 0.0214

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00788

Gnomad4 FIN AF: 0.0272

Gnomad4 NFE AF: 0.0325

Gnomad4 OTH AF: 0.0299

Alfa AF: 0.0273 Hom.: 15

Bravo AF: 0.0249

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 10, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Epidermodysplasia verruciformis Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.7
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.50		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.50		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs143140501; hg19: chr17-76113872;