dbSNP rs35853276: MAP3K20:p.Leu147Leu (chr2-173190918-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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

GnomAD3 exomes

AF:

0.101

AC:

24821

AN:

246928

Hom.:

1725

AF XY:

0.102

AC XY:

13671

AN XY:

133440

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 SAS exome

AF:

0.141

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

Gnomad4 AFR exome

AF:

0.263

Gnomad4 AMR exome

AF:

0.0683

Gnomad4 ASJ exome

AF:

0.172

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.142

Gnomad4 FIN exome

AF:

0.0495

Gnomad4 NFE exome

AF:

0.0908

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.137

AC:

20884

AN:

152200

Hom.:

1928

Cov.:

AF XY:

0.135

AC XY:

10064

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.257

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.0494

Gnomad4 NFE

AF:

0.0959

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.119

Hom.:

655

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

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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