rs9296669
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_138694.4(PKHD1):c.3785C>T(p.Ala1262Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,613,692 control chromosomes in the GnomAD database, including 208,329 homozygotes. 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 Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A1262A) has been classified as Likely benign.
Frequency
Consequence
NM_138694.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKHD1 | NM_138694.4 | c.3785C>T | p.Ala1262Val | missense_variant | 32/67 | ENST00000371117.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKHD1 | ENST00000371117.8 | c.3785C>T | p.Ala1262Val | missense_variant | 32/67 | 1 | NM_138694.4 | P2 | |
PKHD1 | ENST00000340994.4 | c.3785C>T | p.Ala1262Val | missense_variant | 32/61 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.413 AC: 62670AN: 151922Hom.: 15058 Cov.: 31
GnomAD3 exomes AF: 0.479 AC: 119919AN: 250462Hom.: 30767 AF XY: 0.474 AC XY: 64241AN XY: 135514
GnomAD4 exome AF: 0.507 AC: 740864AN: 1461652Hom.: 193271 Cov.: 58 AF XY: 0.504 AC XY: 366300AN XY: 727134
GnomAD4 genome ? AF: 0.412 AC: 62671AN: 152040Hom.: 15058 Cov.: 31 AF XY: 0.409 AC XY: 30424AN XY: 74330
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 18, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 21, 2016 | p.Ala1262Val in exon 32 of PKHD1: This variant is not expected to have clinical significance because it has been identified in 66.59% (7676/11528) of Latino chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs9296669). - |
Autosomal recessive polycystic kidney disease Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | May 11, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Polycystic kidney disease 4 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jun 19, 2021 | - - |
Polycystic kidney disease Benign:1
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | Thec.3785C>T, p.Ala1262Val variant was identified in 46.98% of 56668 control alleles in the Exome Aggregation Consortium (March 14, 2016). According to ACMG guidelines for variant classification based on allele frequency, category BA1, this variant is considered benign and has not been further reviewed (Richards 2015). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 22, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at