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GeneBe

5-56815738-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.165G>A(p.Ala55=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 1,350,956 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 108 hom., cov: 33)
Exomes 𝑓: 0.0018 ( 91 hom. )

Consequence

MAP3K1
NM_005921.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.51
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=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-56815738-G-A is Benign according to our data. Variant chr5-56815738-G-A is described in ClinVar as [Benign]. Clinvar id is 707218.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=-2.51 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 = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAP3K1NM_005921.2 linkuse as main transcriptc.165G>A p.Ala55= synonymous_variant 1/20 ENST00000399503.4
MAP3K1XM_047417218.1 linkuse as main transcriptc.165G>A p.Ala55= synonymous_variant 1/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAP3K1ENST00000399503.4 linkuse as main transcriptc.165G>A p.Ala55= synonymous_variant 1/201 NM_005921.2 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0209
AC:
3144
AN:
150404
Hom.:
106
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0734
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00588
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000209
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000148
Gnomad OTH
AF:
0.0136
GnomAD3 exomes
AF:
0.00173
AC:
104
AN:
60048
Hom.:
5
AF XY:
0.00105
AC XY:
37
AN XY:
35318
show subpopulations
Gnomad AFR exome
AF:
0.0932
Gnomad AMR exome
AF:
0.00252
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000149
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000445
Gnomad OTH exome
AF:
0.00169
GnomAD4 exome
AF:
0.00181
AC:
2171
AN:
1200446
Hom.:
91
Cov.:
31
AF XY:
0.00156
AC XY:
914
AN XY:
586214
show subpopulations
Gnomad4 AFR exome
AF:
0.0735
Gnomad4 AMR exome
AF:
0.00314
Gnomad4 ASJ exome
AF:
0.0000510
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000186
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000387
Gnomad4 OTH exome
AF:
0.00419
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0210
AC:
3162
AN:
150510
Hom.:
108
Cov.:
33
AF XY:
0.0194
AC XY:
1423
AN XY:
73524
show subpopulations
Gnomad4 AFR
AF:
0.0737
Gnomad4 AMR
AF:
0.00581
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:
0.0134
Alfa
AF:
0.00477
Hom.:
3
Bravo
AF:
0.0230

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
-0.42
Cadd
Benign
12
Dann
Benign
0.96
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs189140884; hg19: chr5-56111565; API