Genetic Variant NM_018646.6:c.2202T>C (chr7-142871803-A-G) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_018646.6(TRPV6):c.2202T>C(p.Asn734Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 1,614,038 control chromosomes in the GnomAD database, including 718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.039 ( 154 hom., cov: 33)

Exomes 𝑓: 0.025 ( 564 hom. )

Consequence

TRPV6
NM_018646.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.06

Variant links:

Genes affected

TRPV6 (HGNC:14006): (transient receptor potential cation channel subfamily V member 6) This gene encodes a member of a family of multipass membrane proteins that functions as calcium channels. The encoded protein contains N-terminal ankyrin repeats, which are required for channel assembly and regulation. Translation initiation for this protein occurs at a non-AUG start codon that is decoded as methionine. This gene is situated next to a closely related gene for transient receptor potential cation channel subfamily V member 5 (TRPV5). This locus has experienced positive selection in non-African populations, resulting in several non-synonymous codon differences among individuals of different genetic backgrounds. [provided by RefSeq, Feb 2015]

TRPV6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 7-142871803-A-G is Benign according to our data. Variant chr7-142871803-A-G is described in ClinVar as [Benign]. Clinvar id is 2800936.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV6	NM_018646.6 link	c.2202T>C	p.Asn734Asn	synonymous_variant	Exon 15 of 15	ENST00000359396.9	NP_061116.5	Q9H1D0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRPV6	ENST00000359396.9 link	c.2202T>C	p.Asn734Asn	synonymous_variant	Exon 15 of 15	1	NM_018646.6	ENSP00000352358.5	Q9H1D0-1A0A1X7SBT1
TRPV6	ENST00000485138.5 link	n.1812T>C		non_coding_transcript_exon_variant	Exon 9 of 9	2
TRPV6	ENST00000615386.4 link	n.9843T>C		non_coding_transcript_exon_variant	Exon 12 of 12	2

Frequencies

GnomAD3 genomes

AF:

0.0388

AC:

5899

AN:

152056

Hom.:

152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0836

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0258

Gnomad ASJ

AF:

0.0234

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00472

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0258

Gnomad OTH

AF:

0.0435

GnomAD3 exomes

AF:

0.0226

AC:

5679

AN:

251444

Hom.:

AF XY:

0.0205

AC XY:

2792

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0823

Gnomad AMR exome

AF:

0.0165

Gnomad ASJ exome

AF:

0.0220

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.00350

Gnomad FIN exome

AF:

0.00642

Gnomad NFE exome

AF:

0.0275

Gnomad OTH exome

AF:

0.0267

GnomAD4 exome

AF:

0.0252

AC:

36907

AN:

1461864

Hom.:

564

Cov.:

AF XY:

0.0244

AC XY:

17710

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0846

Gnomad4 AMR exome

AF:

0.0188

Gnomad4 ASJ exome

AF:

0.0212

Gnomad4 EAS exome

AF:

0.00247

Gnomad4 SAS exome

AF:

0.00329

Gnomad4 FIN exome

AF:

0.00693

Gnomad4 NFE exome

AF:

0.0270

Gnomad4 OTH exome

AF:

0.0275

GnomAD4 genome

AF:

0.0388

AC:

5903

AN:

152174

Hom.:

154

Cov.:

AF XY:

0.0359

AC XY:

2669

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0835

Gnomad4 AMR

AF:

0.0258

Gnomad4 ASJ

AF:

0.0234

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00472

Gnomad4 NFE

AF:

0.0258

Gnomad4 OTH

AF:

0.0425

Alfa

AF:

0.0323

Hom.:

Bravo

AF:

0.0429

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0302

EpiControl

AF:

0.0299

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

TRPV6-related disorder

Benign:1

Feb 27, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.5

DANN

Benign

0.56

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