2-173091036-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate
The NM_016653.3(MAP3K20):c.5C>T(p.Ser2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000087 in 1,608,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S2S) has been classified as Likely benign.
Frequency
Consequence
NM_016653.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151716Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000243 AC: 6AN: 247314Hom.: 0 AF XY: 0.0000299 AC XY: 4AN XY: 133952
GnomAD4 exome AF: 0.00000824 AC: 12AN: 1456824Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 724932
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151836Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74204
ClinVar
Submissions by phenotype
not provided Uncertain:2
MAP3K20: PM2 -
This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 2 of the MAP3K20 protein (p.Ser2Leu). This variant is present in population databases (rs565333842, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MAP3K20-related conditions. ClinVar contains an entry for this variant (Variation ID: 1360457). 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 not expected to disrupt MAP3K20 protein function with a negative predictive value of 95%. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at