17-63666955-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002401.5(MAP3K3):c.397C>T(p.His133Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,613,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002401.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000639 AC: 16AN: 250390Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135432
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1460958Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 726850
GnomAD4 genome AF: 0.000184 AC: 28AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74448
ClinVar
Submissions by phenotype
Cerebral cavernous malformations 5 Uncertain:1
A MAP3K3 c.397C>T (p.His133Tyr) variant was identified at a near heterozygous allelic fraction of 46.5%, a frequency which may be consistent with it being of germline origin. This variant, to our knowledge, has not been reported in the medical literature and is only observed on 56/1,613,206 alleles in the general population (gnomAD v4.1.0). Computational predictors suggest that this variant does not impact MAP3K3 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of the MAP3K3 c.397C>T (p.His133Tyr) variant is uncertain at this time. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at