chr5-56815654-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005921.2(MAP3K1):c.81C>T(p.Gly27Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,333,836 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 51 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 89 hom. )

Consequence

MAP3K1
NM_005921.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00300

Publications

1 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:

ENSG00000297204 (HGNC:):

ENSG00000297204 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 5-56815654-C-T is Benign according to our data. Variant chr5-56815654-C-T is described in ClinVar as Benign. ClinVar VariationId is 471696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.003 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005921.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K1	NM_005921.2	MANE Select	c.81C>T	p.Gly27Gly	synonymous	Exon 1 of 20	NP_005912.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K1	ENST00000399503.4	TSL:1 MANE Select	c.81C>T	p.Gly27Gly	synonymous	Exon 1 of 20	ENSP00000382423.3
	ENSG00000297204	ENST00000746113.1		n.-207G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00799

AC:

1210

AN:

151434

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00189

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0593

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00297

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.0177

AC:

674

AN:

38058

AF XY:

0.0123

show subpopulations

Gnomad AFR exome

AF:

0.00186

Gnomad AMR exome

AF:

0.0970

Gnomad ASJ exome

AF:

0.000829

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00258

Gnomad OTH exome

AF:

0.00924

GnomAD4 exome

AF:

0.00434

AC:

5134

AN:

1182294

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

2355

AN XY:

575676

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

24268

American (AMR)

AF:

0.0965

AC:

1510

AN:

15644

Ashkenazi Jewish (ASJ)

AF:

0.000164

AC:

AN:

18296

East Asian (EAS)

AF:

0.00

AC:

AN:

26876

South Asian (SAS)

AF:

0.0000429

AC:

AN:

46640

European-Finnish (FIN)

AF:

0.000235

AC:

AN:

25542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3322

European-Non Finnish (NFE)

AF:

0.00342

AC:

3336

AN:

974188

Other (OTH)

AF:

0.00501

AC:

238

AN:

47518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

239

478

718

957

1196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

162

324

486

648

810

<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:

0.00800

AC:

1213

AN:

151542

Hom.:

Cov.:

AF XY:

0.00856

AC XY:

634

AN XY:

74058

show subpopulations

African (AFR)

AF:

0.00188

AC:

AN:

41436

American (AMR)

AF:

0.0594

AC:

905

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00297

AC:

201

AN:

67780

Other (OTH)

AF:

0.0133

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

114

171

228

285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00589

Hom.:

Bravo

AF:

0.0139

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

46,XY sex reversal 6

Benign:1

Jan 12, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

-0.0030

PromoterAI

0.0082

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over