chr17-45286763-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_003954.5(MAP3K14):c.820C>T(p.Pro274Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 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. P274P) has been classified as Likely benign.
Frequency
Consequence
NM_003954.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP3K14 | NM_003954.5 | c.820C>T | p.Pro274Ser | missense_variant | 5/16 | ENST00000344686.8 | |
MAP3K14 | XM_047436997.1 | c.820C>T | p.Pro274Ser | missense_variant | 5/15 | ||
MAP3K14 | XM_047436998.1 | c.820C>T | p.Pro274Ser | missense_variant | 6/16 | ||
MAP3K14 | XM_011525441.3 | c.820C>T | p.Pro274Ser | missense_variant | 6/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP3K14 | ENST00000344686.8 | c.820C>T | p.Pro274Ser | missense_variant | 5/16 | 1 | NM_003954.5 | P1 | |
MAP3K14 | ENST00000376926.8 | c.820C>T | p.Pro274Ser | missense_variant | 4/15 | 1 | P1 | ||
MAP3K14 | ENST00000617331.3 | c.820C>T | p.Pro274Ser | missense_variant | 6/17 | 5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000407 AC: 1AN: 245400Hom.: 0 AF XY: 0.00000751 AC XY: 1AN XY: 133136
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460172Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726178
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
NIK deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 06, 2018 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with MAP3K14-related disease. This variant is present in population databases (rs747466210, ExAC 0.007%). This sequence change replaces proline with serine at codon 274 of the MAP3K14 protein (p.Pro274Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at