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

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005921.2(MAP3K1):c.2845_2847delACA(p.Thr949del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 1,571,420 control chromosomes in the GnomAD database, including 459,174 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45178 hom., cov: 0)

Exomes 𝑓: 0.77 ( 413996 hom. )

Consequence

MAP3K1
NM_005921.2 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts 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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 5-56882021-TCAA-T is Benign according to our data. Variant chr5-56882021-TCAA-T is described in ClinVar as [Benign]. Clinvar id is 435819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-56882021-TCAA-T is described in Lovd as [Benign]. Variant chr5-56882021-TCAA-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K1	NM_005921.2 linkuse as main transcript	c.2845_2847delACA	p.Thr949del	conservative_inframe_deletion	14/20	ENST00000399503.4	NP_005912.1	Q13233
MAP3K1	XM_047417218.1 linkuse as main transcript	c.2845_2847delACA	p.Thr949del	conservative_inframe_deletion	14/18		XP_047273174.1
MAP3K1	XM_047417219.1 linkuse as main transcript	c.2434_2436delACA	p.Thr812del	conservative_inframe_deletion	15/21		XP_047273175.1
MAP3K1	XM_047417220.1 linkuse as main transcript	c.2434_2436delACA	p.Thr812del	conservative_inframe_deletion	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_2847delACA	p.Thr949del	conservative_inframe_deletion	14/20	1	NM_005921.2	ENSP00000382423.3		Q13233

Frequencies

GnomAD3 genomes

AF:

0.771

AC:

116272

AN:

150860

Hom.:

45126

Cov.:

show subpopulations

Gnomad AFR

AF:

0.742

Gnomad AMI

AF:

0.709

Gnomad AMR

AF:

0.672

Gnomad ASJ

AF:

0.817

Gnomad EAS

AF:

0.574

Gnomad SAS

AF:

0.767

Gnomad FIN

AF:

0.805

Gnomad MID

AF:

0.704

Gnomad NFE

AF:

0.819

Gnomad OTH

AF:

0.770

GnomAD3 exomes

AF:

0.740

AC:

169887

AN:

229430

Hom.:

63153

AF XY:

0.750

AC XY:

92925

AN XY:

123974

show subpopulations

Gnomad AFR exome

AF:

0.730

Gnomad AMR exome

AF:

0.577

Gnomad ASJ exome

AF:

0.806

Gnomad EAS exome

AF:

0.551

Gnomad SAS exome

AF:

0.755

Gnomad FIN exome

AF:

0.791

Gnomad NFE exome

AF:

0.805

Gnomad OTH exome

AF:

0.754

GnomAD4 exome

AF:

0.770

AC:

1093464

AN:

1420440

Hom.:

413996

AF XY:

0.770

AC XY:

544151

AN XY:

707110

show subpopulations

Gnomad4 AFR exome

AF:

0.709

Gnomad4 AMR exome

AF:

0.580

Gnomad4 ASJ exome

AF:

0.791

Gnomad4 EAS exome

AF:

0.553

Gnomad4 SAS exome

AF:

0.743

Gnomad4 FIN exome

AF:

0.778

Gnomad4 NFE exome

AF:

0.789

Gnomad4 OTH exome

AF:

0.755

GnomAD4 genome

AF:

0.771

AC:

116380

AN:

150980

Hom.:

45178

Cov.:

AF XY:

0.765

AC XY:

56417

AN XY:

73700

show subpopulations

Gnomad4 AFR

AF:

0.742

Gnomad4 AMR

AF:

0.671

Gnomad4 ASJ

AF:

0.817

Gnomad4 EAS

AF:

0.575

Gnomad4 SAS

AF:

0.767

Gnomad4 FIN

AF:

0.805

Gnomad4 NFE

AF:

0.819

Gnomad4 OTH

AF:

0.771

Bravo

AF:

0.759

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 19, 2016

- -

46,XY sex reversal 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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