NM_001009944.3:c.5830G>A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PP3_StrongBS2_Supporting
The NM_001009944.3(PKD1):c.5830G>A(p.Gly1944Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,590,506 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001009944.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PKD1 | NM_001009944.3 | c.5830G>A | p.Gly1944Arg | missense_variant | Exon 15 of 46 | ENST00000262304.9 | NP_001009944.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152244Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000179 AC: 41AN: 229354Hom.: 0 AF XY: 0.000181 AC XY: 23AN XY: 127246
GnomAD4 exome AF: 0.000179 AC: 258AN: 1438262Hom.: 1 Cov.: 34 AF XY: 0.000181 AC XY: 129AN XY: 714080
GnomAD4 genome AF: 0.000145 AC: 22AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15AN XY: 74372
ClinVar
Submissions by phenotype
not specified Uncertain:1
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Polycystic kidney disease, adult type Uncertain:1
The missense variant c.5830G>A (p.Gly1944Arg) in PKD1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has been reported to the ClinVar database as Uncertain Significance. The p.Gly1944Arg variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.01764% is reported in gnomAD. The amino acid Gly at position 1944 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Gly1944Arg in PKD1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance . -
not provided Uncertain:1
Observed with a second PKD1 variant in patients with polycystic kidney disease referred for genetic testing at GeneDx and in published literature (Carrera et al., 2016); Identified in an individual with spontaneous coronary artery dissection (Carss et al., 2020); Reported in the unaffected father of a deceased fetus with enlarged hyperechogenic kidneys; however, no fetal DNA was available to confirm the presence of this variant in the fetus. Of note, the fetus's mother with polycystic kidney disease and additional affected maternal relatives harbor a variant in the PKD2 gene (Izzi et al., 2022); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: Izzi_2020_abstract, 27499327, 33125268, 35497784) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at