rs797044713
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_138694.4(PKHD1):โc.3528_3529insCโ(p.Ser1177LeufsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,138 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (โ โ ). Synonymous variant affecting the same amino acid position (i.e. V1176V) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_138694.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKHD1 | NM_138694.4 | c.3528_3529insC | p.Ser1177LeufsTer13 | frameshift_variant | 30/67 | ENST00000371117.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKHD1 | ENST00000371117.8 | c.3528_3529insC | p.Ser1177LeufsTer13 | frameshift_variant | 30/67 | 1 | NM_138694.4 | P2 | |
PKHD1 | ENST00000340994.4 | c.3528_3529insC | p.Ser1177LeufsTer13 | frameshift_variant | 30/61 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251440Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135888
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727242
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74384
ClinVar
Submissions by phenotype
Autosomal recessive polycystic kidney disease Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Feb 26, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2023 | This sequence change creates a premature translational stop signal (p.Ser1177Leufs*13) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant is present in population databases (rs797044713, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 196636). For these reasons, this variant has been classified as Pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 11, 2014 | - - |
Polycystic kidney disease 4 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 28, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at