7-142908799-G-T

Variant names:

• chr7-142908799-G-T
• rs368515580
• NM_019841.7:c.1905C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: TRPV5 NM_019841.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17193493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV5	NM_019841.7	c.1905C>A	p.Asn635Lys	missense_variant	Exon 15 of 15	ENST00000265310.6	NP_062815.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV5	ENST00000265310.6	c.1905C>A	p.Asn635Lys	missense_variant	Exon 15 of 15	1	NM_019841.7	ENSP00000265310.1
TRPV5	ENST00000439304.5	c.1740C>A	p.Asn580Lys	missense_variant	Exon 14 of 14	5		ENSP00000406361.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000121 AC: 3 AN: 247112 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133752

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 SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000891 AC: 13 AN: 1458468 Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 4 AN XY: 725176

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.000183

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1905C>A (p.N635K) alteration is located in exon 15 (coding exon 15) of the TRPV5 gene. This alteration results from a C to A substitution at nucleotide position 1905, causing the asparagine (N) at amino acid position 635 to be replaced by a lysine (K). 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	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.64	T
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.010	N;N
REVEL	Benign	0.17
Sift	Benign	0.033	D;D
Sift4G	Uncertain	0.026	D;D
Vest4		0.096
MutPred		0.50		Gain of ubiquitination at N635 (P = 0.023);.;
MVP		0.79
MPC		0.19
ClinPred		0.14	T
GERP RS		3.0
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs368515580; hg19: chr7-142605965;