rs1419271434

Variant names:

• chr7-142908794-T-C
• rs1419271434
• NM_019841.7:c.1910A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019841.7(TRPV5):​c.1910A>G​(p.Asn637Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 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: 6.9e-7 (0 hom.)
• Consequence: TRPV5 NM_019841.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36
• Publications: 0 publications found

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

ACMG classification

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=0.12182152).

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.1910A>G	p.Asn637Ser	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.1910A>G	p.Asn637Ser	missense	Exon 15 of 15	ENSP00000265310.1	Q9NQA5-1
	TRPV5	ENST00000439304.5	TSL:5	c.1745A>G	p.Asn582Ser	missense	Exon 14 of 14	ENSP00000406361.1	H7C2J6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459282 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725722

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5024

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111066

Other (OTH) AF: 0.00 AC: 0 AN: 60254

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.31
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.70	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.90	T
PhyloP100		2.4
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.21
Sift	Benign	0.15	T
Sift4G	Benign	0.28	T
Vest4		0.042
MutPred		0.31		Gain of sheet (P = 0.1208)
MVP		0.71
MPC		0.12
ClinPred		0.083	T
GERP RS		2.4
gMVP		0.15
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1419271434; hg19: chr7-142605960;