5-56882021-TCAACAACAACAACAA-TCAACAACAACAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:3

Conservation

PhyloP100: 3.28

Publications

23 publications found

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 Gene-Disease associations (from GenCC):

46,XY sex reversal 6
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
breast cancer
Inheritance: AD Classification: MODERATE Submitted by: G2P
46,XY complete gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
46,XY partial gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MAP3K1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 435819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
MAP3K1	NM_005921.2 link	c.2845_2847delACA	p.Thr949del	conservative_inframe_deletion	Exon 14 of 20	ENST00000399503.4	NP_005912.1	Q13233
MAP3K1	XM_047417218.1 link	c.2845_2847delACA	p.Thr949del	conservative_inframe_deletion	Exon 14 of 18		XP_047273174.1
MAP3K1	XM_047417219.1 link	c.2434_2436delACA	p.Thr812del	conservative_inframe_deletion	Exon 15 of 21		XP_047273175.1
MAP3K1	XM_047417220.1 link	c.2434_2436delACA	p.Thr812del	conservative_inframe_deletion	Exon 15 of 21		XP_047273176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K1	ENST00000399503.4 link	c.2845_2847delACA	p.Thr949del	conservative_inframe_deletion	Exon 14 of 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

GnomAD2 exomes

AF:

0.740

AC:

169887

AN:

229430

AF XY:

0.750

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 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

African (AFR)

AF:

0.709

AC:

23240

AN:

32774

American (AMR)

AF:

0.580

AC:

25545

AN:

44024

Ashkenazi Jewish (ASJ)

AF:

0.791

AC:

20185

AN:

25518

East Asian (EAS)

AF:

0.553

AC:

21710

AN:

39240

South Asian (SAS)

AF:

0.743

AC:

62721

AN:

84404

European-Finnish (FIN)

AF:

0.778

AC:

40643

AN:

52228

Middle Eastern (MID)

AF:

0.760

AC:

4300

AN:

5656

European-Non Finnish (NFE)

AF:

0.789

AC:

850655

AN:

1077706

Other (OTH)

AF:

0.755

AC:

44465

AN:

58890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

13726

27453

41179

54906

68632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20180

40360

60540

80720

100900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.771

AC:

116380

AN:

150980

Hom.:

45178

Cov.:

AF XY:

0.765

AC XY:

56417

AN XY:

73700

show subpopulations

African (AFR)

AF:

0.742

AC:

30455

AN:

41030

American (AMR)

AF:

0.671

AC:

10185

AN:

15170

Ashkenazi Jewish (ASJ)

AF:

0.817

AC:

2829

AN:

3462

East Asian (EAS)

AF:

0.575

AC:

2937

AN:

5108

South Asian (SAS)

AF:

0.767

AC:

3671

AN:

4786

European-Finnish (FIN)

AF:

0.805

AC:

8380

AN:

10406

Middle Eastern (MID)

AF:

0.709

AC:

207

AN:

292

European-Non Finnish (NFE)

AF:

0.819

AC:

55461

AN:

67728

Other (OTH)

AF:

0.771

AC:

1617

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1269

2538

3808

5077

6346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

848

1696

2544

3392

4240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.760

Hom.:

4880

Bravo

AF:

0.759

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 19, 2016

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

46,XY sex reversal 6

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.3

Mutation Taster

=82/18

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over