rs146745096
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_138694.4(PKHD1):c.4447G>A(p.Glu1483Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,626 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_138694.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKHD1 | NM_138694.4 | c.4447G>A | p.Glu1483Lys | missense_variant | 32/67 | ENST00000371117.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKHD1 | ENST00000371117.8 | c.4447G>A | p.Glu1483Lys | missense_variant | 32/67 | 1 | NM_138694.4 | P2 | |
PKHD1 | ENST00000340994.4 | c.4447G>A | p.Glu1483Lys | missense_variant | 32/61 | 5 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 250900Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135678
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461316Hom.: 0 Cov.: 35 AF XY: 0.0000151 AC XY: 11AN XY: 726832
GnomAD4 genome AF: 0.000184 AC: 28AN: 152310Hom.: 1 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74480
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 30, 2022 | 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 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 17, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 03, 2022 | - - |
Autosomal recessive polycystic kidney disease Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
PKHD1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 15, 2023 | The PKHD1 c.4447G>A variant is predicted to result in the amino acid substitution p.Glu1483Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.068% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-51890161-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at