Variant 7-142915352-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019841.7(TRPV5):c.1241G>A(p.Arg414His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,606,684 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

TRPV5
NM_019841.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35

Variant links:

Genes affected

TRPV5 (HGNC:3145): (transient receptor potential cation channel subfamily V member 5) This gene is a member of the transient receptor family and the TrpV subfamily. The calcium-selective channel encoded by this gene has 6 transmembrane-spanning domains, multiple potential phosphorylation sites, an N-linked glycosylation site, and 5 ANK repeats. This protein forms homotetramers or heterotetramers and is activated by a low internal calcium level. [provided by RefSeq, Jul 2008]

TRPV5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061428696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV5	NM_019841.7 linkuse as main transcript	c.1241G>A	p.Arg414His	missense_variant	10/15	ENST00000265310.6	NP_062815.3	Q9NQA5A0A0A6YY98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV5	ENST00000265310.6 linkuse as main transcript	c.1241G>A	p.Arg414His	missense_variant	10/15	1	NM_019841.7	ENSP00000265310.1		A0A0A6YY98
TRPV5	ENST00000439304.5 linkuse as main transcript	c.1076G>A	p.Arg359His	missense_variant	9/14	5		ENSP00000406361.1		H7C2J6

Frequencies

GnomAD3 genomes

AF:

0.000704

AC:

107

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.000733

AC:

178

AN:

242878

Hom.:

AF XY:

0.000721

AC XY:

AN XY:

131688

show subpopulations

Gnomad AFR exome

AF:

0.000374

Gnomad AMR exome

AF:

0.000797

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.00119

GnomAD4 exome

AF:

0.00138

AC:

2003

AN:

1454546

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

1002

AN XY:

723880

show subpopulations

Gnomad4 AFR exome

AF:

0.000488

Gnomad4 AMR exome

AF:

0.000814

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00166

Gnomad4 OTH exome

AF:

0.00178

GnomAD4 genome

AF:

0.000703

AC:

107

AN:

152138

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.000844

Hom.:

Bravo

AF:

0.000835

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000675

AC:

EpiCase

AF:

0.00147

EpiControl

AF:

0.00101

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.1241G>A (p.R414H) alteration is located in exon 10 (coding exon 10) of the TRPV5 gene. This alteration results from a G to A substitution at nucleotide position 1241, causing the arginine (R) at amino acid position 414 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

0.075

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;D

Eigen

Benign

-0.044

Eigen_PC

Benign

0.023

FATHMM_MKL

Uncertain

0.82

M_CAP

Benign

0.061

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-0.31

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.7

N;N

REVEL

Uncertain

0.48

Sift

Benign

0.12

T;T

Sift4G

Benign

0.16

T;T

Vest4

0.28

MVP

0.89

MPC

0.24

ClinPred

0.028

GERP RS

3.5

gMVP

0.30

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