17-58216728-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_017777.4(MKS1):c.199C>T(p.Arg67Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000818 in 1,613,964 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R67H) has been classified as Uncertain significance.
Frequency
Consequence
NM_017777.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MKS1 | NM_017777.4 | c.199C>T | p.Arg67Cys | missense_variant | 3/18 | ENST00000393119.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MKS1 | ENST00000393119.7 | c.199C>T | p.Arg67Cys | missense_variant | 3/18 | 1 | NM_017777.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000120 AC: 30AN: 249504Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135368
GnomAD4 exome AF: 0.0000759 AC: 111AN: 1461832Hom.: 0 Cov.: 32 AF XY: 0.0000756 AC XY: 55AN XY: 727210
GnomAD4 genome AF: 0.000138 AC: 21AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74314
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 22, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 15, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Meckel syndrome, type 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 17, 2020 | - - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at