chr12-111880457-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003668.4(MAPKAPK5):c.590C>T(p.Ala197Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,462 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003668.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151964Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249268Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135232
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461498Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 727044
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151964Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74194
ClinVar
Submissions by phenotype
Syndromic disease Uncertain:1
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with developmental disorder (PMID: 33442026). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from alanine to valine. (I) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (1 heterozygote, 0 homozygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and very highly conserved with a minor amino acid change. (I) 0600 - Variant is located in the annotated catalytic domain (PMID: 33442026). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1209 - This variant has been shown to be both maternally and paternally inherited (biallelic) (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at