rs201599080

Variant names:

• chr7-142908693-C-A
• rs201599080
• NM_019841.7:c.2011G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-142908693-C-A
• chr7-142908693-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019841.7(TRPV5):​c.2011G>T​(p.Ala671Ser) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A671T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRPV5 NM_019841.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048669904).

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.2011G>T	p.Ala671Ser	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.2011G>T	p.Ala671Ser	missense	Exon 15 of 15	ENSP00000265310.1	Q9NQA5-1
	TRPV5	ENST00000439304.5	TSL:5	c.1846G>T	p.Ala616Ser	missense	Exon 14 of 14	ENSP00000406361.1	H7C2J6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.10
DANN	Benign	0.17
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.047	N
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.83	T
PhyloP100		-0.60
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.15
Sift	Benign	0.88	T
Sift4G	Benign	0.86	T
Vest4		0.11
MutPred		0.13		Gain of phosphorylation at A671 (P = 0.0106)
MVP		0.52
MPC		0.14
ClinPred		0.038	T
GERP RS		-7.2
gMVP		0.11
Mutation Taster		=99/1	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: rs201599080; hg19: chr7-142605859;