rs972049140
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001009944.3(PKD1):c.74G>T(p.Gly25Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000586 in 981,904 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. GP25D?) has been classified as Pathogenic.
Frequency
Consequence
NM_001009944.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD1 | NM_001009944.3 | c.74G>T | p.Gly25Val | missense_variant | 1/46 | ENST00000262304.9 | |
PKD1 | NM_000296.4 | c.74G>T | p.Gly25Val | missense_variant | 1/46 | ||
PKD1 | XM_047434208.1 | c.74G>T | p.Gly25Val | missense_variant | 1/48 | ||
PKD1 | XM_047434209.1 | c.74G>T | p.Gly25Val | missense_variant | 1/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD1 | ENST00000262304.9 | c.74G>T | p.Gly25Val | missense_variant | 1/46 | 1 | NM_001009944.3 | P5 | |
PKD1 | ENST00000423118.5 | c.74G>T | p.Gly25Val | missense_variant | 1/46 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000437 AC: 64AN: 146620Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.000613 AC: 512AN: 835190Hom.: 1 Cov.: 16 AF XY: 0.000652 AC XY: 253AN XY: 388074
GnomAD4 genome ? AF: 0.000429 AC: 63AN: 146714Hom.: 0 Cov.: 31 AF XY: 0.000392 AC XY: 28AN XY: 71414
ClinVar
Submissions by phenotype
Autosomal dominant polycystic kidney disease Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research | Jan 01, 2019 | - - |
PKD1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 01, 2023 | The PKD1 c.74G>T variant is predicted to result in the amino acid substitution p.Gly25Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.050% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2185617-C-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 18, 2019 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 20, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at