rs1131692053
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_005921.2(MAP3K1):c.634-8T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
MAP3K1
NM_005921.2 splice_region, splice_polypyrimidine_tract, intron
NM_005921.2 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.9999
2
Clinical Significance
Conservation
PhyloP100: 0.652
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 5-56859707-T-A is Pathogenic according to our data. Variant chr5-56859707-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 30144.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-56859707-T-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAP3K1 | NM_005921.2 | c.634-8T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000399503.4 | |||
MAP3K1 | XM_047417218.1 | c.634-8T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
MAP3K1 | XM_047417219.1 | c.223-8T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
MAP3K1 | XM_047417220.1 | c.223-8T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAP3K1 | ENST00000399503.4 | c.634-8T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005921.2 | P1 | |||
ENST00000415589.1 | n.298A>T | non_coding_transcript_exon_variant | 2/4 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
46,XY sex reversal 6 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 10, 2010 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
DS_AL_spliceai
Position offset: 8
Find out detailed SpliceAI scores and Pangolin per-transcript scores at