rs2229883
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_005921.2(MAP3K1):c.1917G>A(p.Leu639=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,614,132 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0073 ( 21 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 10 hom. )
Consequence
MAP3K1
NM_005921.2 synonymous
NM_005921.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.401
Genes affected
MAP3K1 (HGNC:6848): (mitogen-activated protein kinase kinase kinase 1) The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 5-56875262-G-A is Benign according to our data. Variant chr5-56875262-G-A is described in ClinVar as [Benign]. Clinvar id is 539065.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.401 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00733 (1116/152292) while in subpopulation AFR AF= 0.0242 (1005/41548). AF 95% confidence interval is 0.0229. There are 21 homozygotes in gnomad4. There are 525 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1116 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP3K1 | NM_005921.2 | c.1917G>A | p.Leu639= | synonymous_variant | 10/20 | ENST00000399503.4 | |
MAP3K1 | XM_047417218.1 | c.1917G>A | p.Leu639= | synonymous_variant | 10/18 | ||
MAP3K1 | XM_047417219.1 | c.1506G>A | p.Leu502= | synonymous_variant | 11/21 | ||
MAP3K1 | XM_047417220.1 | c.1506G>A | p.Leu502= | synonymous_variant | 11/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP3K1 | ENST00000399503.4 | c.1917G>A | p.Leu639= | synonymous_variant | 10/20 | 1 | NM_005921.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00732 AC: 1114AN: 152174Hom.: 21 Cov.: 32
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GnomAD3 exomes AF: 0.00237 AC: 591AN: 249292Hom.: 9 AF XY: 0.00171 AC XY: 231AN XY: 135218
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GnomAD4 exome AF: 0.00113 AC: 1653AN: 1461840Hom.: 10 Cov.: 32 AF XY: 0.000991 AC XY: 721AN XY: 727220
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GnomAD4 genome ? AF: 0.00733 AC: 1116AN: 152292Hom.: 21 Cov.: 32 AF XY: 0.00705 AC XY: 525AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
46,XY sex reversal 6 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at