Variant 7-142871948-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018646.6(TRPV6):c.2057G>A(p.Arg686His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,457,706 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TRPV6
NM_018646.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV6	NM_018646.6 linkuse as main transcript	c.2057G>A	p.Arg686His	missense_variant	15/15	ENST00000359396.9	NP_061116.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV6	ENST00000359396.9 linkuse as main transcript	c.2057G>A	p.Arg686His	missense_variant	15/15	1	NM_018646.6	ENSP00000352358	P5	Q9H1D0-1
TRPV6	ENST00000485138.5 linkuse as main transcript	n.1667G>A		non_coding_transcript_exon_variant	9/9	2
TRPV6	ENST00000615386.4 linkuse as main transcript	n.9698G>A		non_coding_transcript_exon_variant	12/12	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1457706

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

724716

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.1937G>A (p.R646H) alteration is located in exon 15 (coding exon 15) of the TRPV6 gene. This alteration results from a G to A substitution at nucleotide position 1937, causing the arginine (R) at amino acid position 646 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

0.00030

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.59

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.5

N;.

REVEL

Benign

0.12

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.0090

D;.

Vest4

0.10

MVP

0.80

MPC

0.36

ClinPred

0.92

GERP RS

5.5

Varity_R

0.46

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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