rs9381994
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_138694.4(PKHD1):āc.12143A>Gā(p.Gln4048Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,613,906 control chromosomes in the GnomAD database, including 248,948 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 Benign (ā ā ).
Frequency
Consequence
NM_138694.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.12143A>G | p.Gln4048Arg | missense_variant | 67/67 | ENST00000371117.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKHD1 | ENST00000371117.8 | c.12143A>G | p.Gln4048Arg | missense_variant | 67/67 | 1 | NM_138694.4 | P2 | |
ENST00000589278.6 | n.811-3197T>C | intron_variant, non_coding_transcript_variant | 5 | ||||||
ENST00000454361.1 | n.81-3192T>C | intron_variant, non_coding_transcript_variant | 3 | ||||||
ENST00000650088.1 | n.222-3192T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.533 AC: 81013AN: 152104Hom.: 21711 Cov.: 35
GnomAD3 exomes AF: 0.566 AC: 142135AN: 250914Hom.: 40633 AF XY: 0.566 AC XY: 76708AN XY: 135618
GnomAD4 exome AF: 0.556 AC: 813130AN: 1461684Hom.: 227239 Cov.: 52 AF XY: 0.558 AC XY: 406037AN XY: 727146
GnomAD4 genome AF: 0.532 AC: 81035AN: 152222Hom.: 21709 Cov.: 35 AF XY: 0.532 AC XY: 39565AN XY: 74412
ClinVar
Submissions by phenotype
Autosomal recessive polycystic kidney disease Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | May 11, 2017 | - - |
Polycystic kidney disease 4 Benign:3
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 25, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jun 19, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 27, 2015 | - - |
Polycystic kidney disease Benign:1
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | Thec.12143A>G, p.Gln4048Arg variant was identified in 56.3% of 68262 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 29, 2019 | This variant is associated with the following publications: (PMID: 28509106) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at