rs730882120
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_017777.4(MKS1):āc.1382A>Gā(p.Tyr461Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. Y461Y) has been classified as Likely benign.
Frequency
Consequence
NM_017777.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MKS1 | NM_017777.4 | c.1382A>G | p.Tyr461Cys | missense_variant | 15/18 | ENST00000393119.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MKS1 | ENST00000393119.7 | c.1382A>G | p.Tyr461Cys | missense_variant | 15/18 | 1 | NM_017777.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249530Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135390
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727246
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome 13 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2014 | - - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 03, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 461 of the MKS1 protein (p.Tyr461Cys). This variant is present in population databases (rs730882120, gnomAD 0.007%). This missense change has been observed in individual(s) with MKS1-related conditions (PMID: 24608809). ClinVar contains an entry for this variant (Variation ID: 183011). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MKS1 protein function. 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. - |
Bardet-Biedl syndrome 13;C3714506:Meckel syndrome, type 1;C4310705:Joubert syndrome 28 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Oct 18, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at