rs1480119769

Variant names:

• chr7-142908798-G-A
• rs1480119769
• NM_019841.7:c.1906C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-142908798-G-A
• chr7-142908798-G-T

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.1906C>T​(p.His636Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: TRPV5 NM_019841.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24
• 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=0.14107719).

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.1906C>T	p.His636Tyr	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.1906C>T	p.His636Tyr	missense	Exon 15 of 15	ENSP00000265310.1	Q9NQA5-1
	TRPV5	ENST00000439304.5	TSL:5	c.1741C>T	p.His581Tyr	missense	Exon 14 of 14	ENSP00000406361.1	H7C2J6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.081
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.65	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.77	T
PhyloP100		1.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.21
Sift	Benign	0.059	T
Sift4G	Uncertain	0.013	D
Vest4		0.090
MutPred		0.30		Gain of phosphorylation at H636 (P = 0.0564)
MVP		0.79
MPC		0.18
ClinPred		0.18	T
GERP RS		0.91
gMVP		0.44
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1480119769; hg19: chr7-142605964;