chr7-142909593-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_019841.7(TRPV5):c.1792G>A(p.Val598Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,613,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Consequence
NM_019841.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRPV5 | NM_019841.7 | c.1792G>A | p.Val598Met | missense_variant | Exon 14 of 15 | ENST00000265310.6 | NP_062815.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRPV5 | ENST00000265310.6 | c.1792G>A | p.Val598Met | missense_variant | Exon 14 of 15 | 1 | NM_019841.7 | ENSP00000265310.1 | ||
TRPV5 | ENST00000439304.5 | c.1627G>A | p.Val543Met | missense_variant | Exon 13 of 14 | 5 | ENSP00000406361.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249776Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135124
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461448Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727030
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74412
ClinVar
Submissions by phenotype
Renal Calcium Wasting Hypercalciuria Pathogenic:1
The p.Val598Met variant is found in a family of 8 with 3 affected individuals (each has hypercalciuria). The variant is heterozygous in only 4 individuals in gnomAD and is not found in homozygosity in large population databases. Additional homozygosity mapping has excluded 98.85% of the genome for Identity-by-decent. Additional in vitro cell models show that cells transfected with p.Val598Met have lower calcium permeability and surface channel expression compared to cells transfected with the wild-type protein. The mutant protein also undergoes proteasomal degradation. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at