rs702689

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005921.2(MAP3K1):c.2416G>A(p.Asp806Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,612,860 control chromosomes in the GnomAD database, including 374,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 29280 hom., cov: 31)

Exomes 𝑓: 0.68 ( 345418 hom. )

Consequence

MAP3K1
NM_005921.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 8.19

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]

MAP3K1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4606336E-5).

BP6

Variant 5-56881616-G-A is Benign according to our data. Variant chr5-56881616-G-A is described in ClinVar as [Benign]. Clinvar id is 518364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-56881616-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K1	NM_005921.2 link	c.2416G>A	p.Asp806Asn	missense_variant	14/20	ENST00000399503.4	NP_005912.1	Q13233
MAP3K1	XM_047417218.1 link	c.2416G>A	p.Asp806Asn	missense_variant	14/18		XP_047273174.1
MAP3K1	XM_047417219.1 link	c.2005G>A	p.Asp669Asn	missense_variant	15/21		XP_047273175.1
MAP3K1	XM_047417220.1 link	c.2005G>A	p.Asp669Asn	missense_variant	15/21		XP_047273176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K1	ENST00000399503.4 link	c.2416G>A	p.Asp806Asn	missense_variant	14/20	1	NM_005921.2	ENSP00000382423.3		Q13233

Frequencies

GnomAD3 genomes

AF:

0.607

AC:

92147

AN:

151850

Hom.:

29262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.629

Gnomad AMR

AF:

0.498

Gnomad ASJ

AF:

0.721

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.721

Gnomad MID

AF:

0.583

Gnomad NFE

AF:

0.716

Gnomad OTH

AF:

0.628

GnomAD3 exomes

AF:

0.594

AC:

147940

AN:

249066

Hom.:

47342

AF XY:

0.603

AC XY:

81451

AN XY:

135130

show subpopulations

Gnomad AFR exome

AF:

0.490

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.728

Gnomad EAS exome

AF:

0.206

Gnomad SAS exome

AF:

0.499

Gnomad FIN exome

AF:

0.722

Gnomad NFE exome

AF:

0.712

Gnomad OTH exome

AF:

0.632

GnomAD4 exome

AF:

0.678

AC:

990820

AN:

1460892

Hom.:

345418

Cov.:

AF XY:

0.674

AC XY:

490099

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.486

Gnomad4 AMR exome

AF:

0.425

Gnomad4 ASJ exome

AF:

0.729

Gnomad4 EAS exome

AF:

0.236

Gnomad4 SAS exome

AF:

0.505

Gnomad4 FIN exome

AF:

0.719

Gnomad4 NFE exome

AF:

0.722

Gnomad4 OTH exome

AF:

0.649

GnomAD4 genome

AF:

0.607

AC:

92200

AN:

151968

Hom.:

29280

Cov.:

AF XY:

0.600

AC XY:

44550

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.490

Gnomad4 AMR

AF:

0.498

Gnomad4 ASJ

AF:

0.721

Gnomad4 EAS

AF:

0.232

Gnomad4 SAS

AF:

0.482

Gnomad4 FIN

AF:

0.721

Gnomad4 NFE

AF:

0.716

Gnomad4 OTH

AF:

0.623

Alfa

AF:

0.681

Hom.:

91833

Bravo

AF:

0.585

TwinsUK

AF:

0.724

AC:

2684

ALSPAC

AF:

0.722

AC:

2782

ESP6500AA

AF:

0.495

AC:

1844

ESP6500EA

AF:

0.721

AC:

5908

ExAC

AF:

0.598

AC:

72226

Asia WGS

AF:

0.379

AC:

1319

AN:

3478

EpiCase

AF:

0.711

EpiControl

AF:

0.710

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

46,XY sex reversal 6

Benign:3

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Nov 02, 2017	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 22468730, 24497709) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

Eigen

Pathogenic

0.68

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.000015

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.10

REVEL

Benign

0.15

Sift

Benign

0.20

Sift4G

Benign

0.65

Polyphen

1.0

Vest4

0.33

MPC

0.26

ClinPred

0.044

GERP RS

5.6

Varity_R

0.37

gMVP

0.46

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over