rs35853276

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016653.3(MAP3K20):c.439T>C(p.Leu147Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 1,596,050 control chromosomes in the GnomAD database, including 9,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1928 hom., cov: 32)

Exomes 𝑓: 0.096 ( 8004 hom. )

Consequence

MAP3K20
NM_016653.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.949

Publications

7 publications found

Variant links:

Genes affected

MAP3K20 (HGNC:17797): (mitogen-activated protein kinase kinase kinase 20) This gene is a member of the MAPKKK family of signal transduction molecules and encodes a protein with an N-terminal kinase catalytic domain, followed by a leucine zipper motif and a sterile-alpha motif (SAM). This magnesium-binding protein forms homodimers and is located in the cytoplasm. The protein mediates gamma radiation signaling leading to cell cycle arrest and activity of this protein plays a role in cell cycle checkpoint regulation in cells. The protein also has pro-apoptotic activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

MAP3K20 links:

MAP3K20-AS1 (HGNC:27935): (MAP3K20 antisense RNA 1)

MAP3K20-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 2-173190918-T-C is Benign according to our data. Variant chr2-173190918-T-C is described in ClinVar as Benign. ClinVar VariationId is 1174343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.949 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K20	NM_016653.3 link	c.439T>C	p.Leu147Leu	synonymous_variant	Exon 6 of 20	ENST00000375213.8	NP_057737.2	Q9NYL2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K20	ENST00000375213.8 link	c.439T>C	p.Leu147Leu	synonymous_variant	Exon 6 of 20	1	NM_016653.3	ENSP00000364361.3		Q9NYL2-1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20859

AN:

152082

Hom.:

1926

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.0494

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.0958

Gnomad OTH

AF:

0.138

GnomAD2 exomes

AF:

0.101

AC:

24821

AN:

246928

AF XY:

0.102

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.0627

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.000440

Gnomad FIN exome

AF:

0.0501

Gnomad NFE exome

AF:

0.0982

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.0959

AC:

138396

AN:

1443850

Hom.:

8004

Cov.:

AF XY:

0.0981

AC XY:

70528

AN XY:

718852

show subpopulations

African (AFR)

AF:

0.263

AC:

8537

AN:

32420

American (AMR)

AF:

0.0683

AC:

2997

AN:

43854

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

4441

AN:

25782

East Asian (EAS)

AF:

0.000328

AC:

AN:

39612

South Asian (SAS)

AF:

0.142

AC:

12014

AN:

84534

European-Finnish (FIN)

AF:

0.0495

AC:

2640

AN:

53324

Middle Eastern (MID)

AF:

0.225

AC:

1267

AN:

5640

European-Non Finnish (NFE)

AF:

0.0908

AC:

99747

AN:

1099046

Other (OTH)

AF:

0.113

AC:

6740

AN:

59638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

5588

11176

16765

22353

27941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3616

7232

10848

14464

18080

<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:

0.137

AC:

20884

AN:

152200

Hom.:

1928

Cov.:

AF XY:

0.135

AC XY:

10064

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.257

AC:

10651

AN:

41492

American (AMR)

AF:

0.100

AC:

1533

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

584

AN:

3468

East Asian (EAS)

AF:

0.000964

AC:

AN:

5186

South Asian (SAS)

AF:

0.135

AC:

652

AN:

4822

European-Finnish (FIN)

AF:

0.0494

AC:

524

AN:

10612

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0959

AC:

6518

AN:

68002

Other (OTH)

AF:

0.138

AC:

291

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

882

1763

2645

3526

4408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.120

Hom.:

685

Bravo

AF:

0.146

Asia WGS

AF:

0.0730

AC:

255

AN:

3478

EpiCase

AF:

0.118

EpiControl

AF:

0.113

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

MAP3K20-related disorder

Benign:1

Oct 24, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.2

(source)

DANN

Benign

0.87

PhyloP100

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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