rs149874529
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001009944.3(PKD1):c.4654G>A(p.Val1552Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,611,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. V1552V) has been classified as Likely benign.
Frequency
Consequence
NM_001009944.3 missense
Scores
Clinical Significance
Conservation
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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.4654G>A | p.Val1552Ile | missense_variant | 15/46 | ENST00000262304.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD1 | ENST00000262304.9 | c.4654G>A | p.Val1552Ile | missense_variant | 15/46 | 1 | NM_001009944.3 | P5 |
Frequencies
GnomAD3 genomes AF: 0.00110 AC: 167AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000218 AC: 54AN: 248018Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 134944
GnomAD4 exome AF: 0.000116 AC: 169AN: 1459538Hom.: 0 Cov.: 36 AF XY: 0.0000992 AC XY: 72AN XY: 726114
GnomAD4 genome AF: 0.00112 AC: 170AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.00114 AC XY: 85AN XY: 74488
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 01, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 01, 2021 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
PKD1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 08, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at