rs730880500
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_002755.4(MAP2K1):c.1168G>A(p.Ala390Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002755.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP2K1 | NM_002755.4 | c.1168G>A | p.Ala390Thr | missense_variant | 11/11 | ENST00000307102.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP2K1 | ENST00000307102.10 | c.1168G>A | p.Ala390Thr | missense_variant | 11/11 | 1 | NM_002755.4 | P1 | |
ENST00000565387.2 | n.225C>T | non_coding_transcript_exon_variant | 2/2 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251304Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135858
GnomAD4 exome AF: 0.000177 AC: 258AN: 1461748Hom.: 0 Cov.: 30 AF XY: 0.000153 AC XY: 111AN XY: 727202
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74334
ClinVar
Submissions by phenotype
MAP2K1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 13, 2023 | The MAP2K1 c.1168G>A variant is predicted to result in the amino acid substitution p.Ala390Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.014% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-66782939-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
RASopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 390 of the MAP2K1 protein (p.Ala390Thr). This variant is present in population databases (rs730880500, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MAP2K1-related conditions. ClinVar contains an entry for this variant (Variation ID: 180900). 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 MAP2K1 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 18, 2020 | This variant is associated with the following publications: (PMID: 29340109) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at