rs909331529
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015488.5(PNKD):āc.370A>Gā(p.Ile124Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000869 in 1,611,492 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I124N) has been classified as Uncertain significance.
Frequency
Consequence
NM_015488.5 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 |
---|---|---|---|---|---|---|---|
PNKD | NM_015488.5 | c.370A>G | p.Ile124Val | missense_variant | 4/10 | ENST00000273077.9 | |
CATIP-AS2 | NR_125777.1 | n.120+11114T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNKD | ENST00000273077.9 | c.370A>G | p.Ile124Val | missense_variant | 4/10 | 1 | NM_015488.5 | ||
CATIP-AS2 | ENST00000411433.1 | n.120+11114T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000660 AC: 1AN: 151604Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251314Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135904
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1459888Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726416
GnomAD4 genome ? AF: 0.00000660 AC: 1AN: 151604Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 73994
ClinVar
Submissions by phenotype
Paroxysmal nonkinesigenic dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 10, 2017 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PNKD-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with valine at codon 124 of the PNKD protein (p.Ile124Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at