Genetic Variant TRPV5:p.Asn635Lys (chr7-142908799-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019841.7(TRPV5):c.1905C>A(p.Asn635Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,458,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TRPV5
NM_019841.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hypercalciuria, absorptive, 2
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

TRPV5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17193493).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019841.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV5	NM_019841.7	MANE Select	c.1905C>A	p.Asn635Lys	missense	Exon 15 of 15	NP_062815.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV5	ENST00000265310.6	TSL:1 MANE Select	c.1905C>A	p.Asn635Lys	missense	Exon 15 of 15	ENSP00000265310.1	Q9NQA5-1
	TRPV5	ENST00000439304.5	TSL:5	c.1740C>A	p.Asn580Lys	missense	Exon 14 of 14	ENSP00000406361.1	H7C2J6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

247112

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1458468

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33384

American (AMR)

AF:

0.00

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4926

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110622

Other (OTH)

AF:

0.000183

AC:

AN:

60218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.17

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.91

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.64

PhyloP100

1.8

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.010

REVEL

Benign

0.17

Sift

Benign

0.033

Sift4G

Uncertain

0.026

Vest4

0.096

MutPred

0.50

Gain of ubiquitination at N635 (P = 0.023)

MVP

0.79

MPC

0.19

ClinPred

0.14

GERP RS

3.0

gMVP

0.41

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over