rs762182665
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_003954.5(MAP3K14):c.296G>A(p.Arg99His) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R99C) has been classified as Uncertain significance.
Frequency
Consequence
NM_003954.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP3K14 | NM_003954.5 | c.296G>A | p.Arg99His | missense_variant | 3/16 | ENST00000344686.8 | |
MAP3K14 | XM_047436997.1 | c.296G>A | p.Arg99His | missense_variant | 3/15 | ||
MAP3K14 | XM_047436998.1 | c.296G>A | p.Arg99His | missense_variant | 4/16 | ||
MAP3K14 | XM_011525441.3 | c.296G>A | p.Arg99His | missense_variant | 4/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP3K14 | ENST00000344686.8 | c.296G>A | p.Arg99His | missense_variant | 3/16 | 1 | NM_003954.5 | P1 | |
MAP3K14 | ENST00000376926.8 | c.296G>A | p.Arg99His | missense_variant | 2/15 | 1 | P1 | ||
MAP3K14 | ENST00000617331.3 | c.296G>A | p.Arg99His | missense_variant | 4/17 | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152152Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249290Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135244
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461640Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13AN XY: 727102
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152152Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74322
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 22, 2023 | The c.296G>A (p.R99H) alteration is located in exon 3 (coding exon 2) of the MAP3K14 gene. This alteration results from a G to A substitution at nucleotide position 296, causing the arginine (R) at amino acid position 99 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
NIK deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 19, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 99 of the MAP3K14 protein (p.Arg99His). This variant is present in population databases (rs762182665, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MAP3K14-related conditions. ClinVar contains an entry for this variant (Variation ID: 544320). 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