chr7-142912589-C-G

Variant names:

• chr7-142912589-C-G
• NM_019841.7:c.1681G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019841.7(TRPV5):​c.1681G>C​(p.Ala561Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRPV5 NM_019841.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.551

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV5	NM_019841.7	c.1681G>C	p.Ala561Pro	missense_variant	Exon 13 of 15	ENST00000265310.6	NP_062815.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV5	ENST00000265310.6	c.1681G>C	p.Ala561Pro	missense_variant	Exon 13 of 15	1	NM_019841.7	ENSP00000265310.1
TRPV5	ENST00000439304.5	c.1516G>C	p.Ala506Pro	missense_variant	Exon 12 of 14	5		ENSP00000406361.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 727248

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1681G>C (p.A561P) alteration is located in exon 13 (coding exon 13) of the TRPV5 gene. This alteration results from a G to C substitution at nucleotide position 1681, causing the alanine (A) at amino acid position 561 to be replaced by a proline (P). 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	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;D
Eigen	Benign	0.091
Eigen_PC	Benign	-0.051
FATHMM_MKL	Benign	0.28	N
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Uncertain	0.24	D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.61
Sift	Benign	0.082	T;T
Sift4G	Benign	0.20	T;T
Vest4		0.80
MutPred		0.69		Loss of stability (P = 0.0517);.;
MVP		0.95
MPC		0.73
ClinPred		0.91	D
GERP RS		4.0
gMVP		0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-142609755;