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GeneBe

5-56815618-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_005921.2(MAP3K1):c.45G>A(p.Pro15=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,311,048 control chromosomes in the GnomAD database, including 184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 105 hom., cov: 33)
Exomes 𝑓: 0.0017 ( 79 hom. )

Consequence

MAP3K1
NM_005921.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.78
Variant links:
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 -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-56815618-G-A is Benign according to our data. Variant chr5-56815618-G-A is described in ClinVar as [Benign]. Clinvar id is 1168726.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.78 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAP3K1NM_005921.2 linkuse as main transcriptc.45G>A p.Pro15= synonymous_variant 1/20 ENST00000399503.4
MAP3K1XM_047417218.1 linkuse as main transcriptc.45G>A p.Pro15= synonymous_variant 1/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAP3K1ENST00000399503.4 linkuse as main transcriptc.45G>A p.Pro15= synonymous_variant 1/201 NM_005921.2 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0208
AC:
3134
AN:
151016
Hom.:
103
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0731
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00579
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000148
Gnomad OTH
AF:
0.0135
GnomAD3 exomes
AF:
0.00207
AC:
46
AN:
22208
Hom.:
1
AF XY:
0.00122
AC XY:
17
AN XY:
13928
show subpopulations
Gnomad AFR exome
AF:
0.112
Gnomad AMR exome
AF:
0.00441
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000118
Gnomad OTH exome
AF:
0.00181
GnomAD4 exome
AF:
0.00172
AC:
1995
AN:
1159920
Hom.:
79
Cov.:
31
AF XY:
0.00151
AC XY:
849
AN XY:
562730
show subpopulations
Gnomad4 AFR exome
AF:
0.0731
Gnomad4 AMR exome
AF:
0.00381
Gnomad4 ASJ exome
AF:
0.0000591
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000210
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000363
Gnomad4 OTH exome
AF:
0.00390
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0209
AC:
3152
AN:
151128
Hom.:
105
Cov.:
33
AF XY:
0.0193
AC XY:
1425
AN XY:
73858
show subpopulations
Gnomad4 AFR
AF:
0.0734
Gnomad4 AMR
AF:
0.00572
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000148
Gnomad4 OTH
AF:
0.0133
Alfa
AF:
0.0179
Hom.:
9
Bravo
AF:
0.0230
Asia WGS
AF:
0.00439
AC:
15
AN:
3430

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 submitterclinical testingInvitaeDec 02, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
Cadd
Benign
15
Dann
Benign
0.97

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs192120973; hg19: chr5-56111445; API