Variant 5-56882021-TCAACAACAACAACAA-TCAACAACAACAACAACAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_005921.2(MAP3K1):c.2845_2847dupACA(p.Thr949dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00085 ( 1 hom. )

Consequence

MAP3K1
NM_005921.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.28

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 5-56882021-T-TCAA is Benign according to our data. Variant chr5-56882021-T-TCAA is described in ClinVar as [Likely_benign]. Clinvar id is 1954893.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K1	NM_005921.2 linkuse as main transcript	c.2845_2847dupACA	p.Thr949dup	conservative_inframe_insertion	14/20	ENST00000399503.4	NP_005912.1	Q13233
MAP3K1	XM_047417218.1 linkuse as main transcript	c.2845_2847dupACA	p.Thr949dup	conservative_inframe_insertion	14/18		XP_047273174.1
MAP3K1	XM_047417219.1 linkuse as main transcript	c.2434_2436dupACA	p.Thr812dup	conservative_inframe_insertion	15/21		XP_047273175.1
MAP3K1	XM_047417220.1 linkuse as main transcript	c.2434_2436dupACA	p.Thr812dup	conservative_inframe_insertion	15/21		XP_047273176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K1	ENST00000399503.4 linkuse as main transcript	c.2845_2847dupACA	p.Thr949dup	conservative_inframe_insertion	14/20	1	NM_005921.2	ENSP00000382423.3		Q13233

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

113

AN:

150946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000366

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00191

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000781

Gnomad SAS

AF:

0.000833

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000856

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.000597

AC:

137

AN:

229430

Hom.:

AF XY:

0.000557

AC XY:

AN XY:

123974

show subpopulations

Gnomad AFR exome

AF:

0.000693

Gnomad AMR exome

AF:

0.000923

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000996

Gnomad SAS exome

AF:

0.000250

Gnomad FIN exome

AF:

0.0000508

Gnomad NFE exome

AF:

0.000680

Gnomad OTH exome

AF:

0.000358

GnomAD4 exome

AF:

0.000852

AC:

1211

AN:

1421414

Hom.:

Cov.:

AF XY:

0.000824

AC XY:

583

AN XY:

707620

show subpopulations

Gnomad4 AFR exome

AF:

0.000610

Gnomad4 AMR exome

AF:

0.000929

Gnomad4 ASJ exome

AF:

0.0000784

Gnomad4 EAS exome

AF:

0.000584

Gnomad4 SAS exome

AF:

0.000249

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.000965

Gnomad4 OTH exome

AF:

0.00107

GnomAD4 genome

AF:

0.000748

AC:

113

AN:

151064

Hom.:

Cov.:

AF XY:

0.000651

AC XY:

AN XY:

73744

show subpopulations

Gnomad4 AFR

AF:

0.000365

Gnomad4 AMR

AF:

0.00191

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000782

Gnomad4 SAS

AF:

0.000834

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000856

Gnomad4 OTH

AF:

0.00143

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MAP3K1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 19, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

46,XY sex reversal 6

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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