Variant 1-233376030-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000366624.8(MAP3K21):c.1790C>T(p.Ser597Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,608,574 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 6 hom. )

Consequence

MAP3K21
ENST00000366624.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.49

Variant links:

Genes affected

MAP3K21 (HGNC:29798): (mitogen-activated protein kinase kinase kinase 21) Predicted to enable protein homodimerization activity and protein kinase activity. Predicted to be involved in protein autophosphorylation and signal transduction. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MAP3K21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027572572).

BP6

Variant 1-233376030-C-T is Benign according to our data. Variant chr1-233376030-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640090.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K21	NM_032435.3 linkuse as main transcript	c.1790C>T	p.Ser597Phe	missense_variant	7/10	ENST00000366624.8	NP_115811.2	Q5TCX8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K21	ENST00000366624.8 linkuse as main transcript	c.1790C>T	p.Ser597Phe	missense_variant	7/10	1	NM_032435.3	ENSP00000355583.3		Q5TCX8-1
MAP3K21	ENST00000366622.1 linkuse as main transcript	c.128C>T	p.Ser43Phe	missense_variant	1/4	1		ENSP00000355581.1		Q5TCX8-3

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

364

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00509

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00316

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00246

AC:

603

AN:

245202

Hom.:

AF XY:

0.00253

AC XY:

336

AN XY:

132788

show subpopulations

Gnomad AFR exome

AF:

0.000573

Gnomad AMR exome

AF:

0.00103

Gnomad ASJ exome

AF:

0.00391

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000346

Gnomad FIN exome

AF:

0.00477

Gnomad NFE exome

AF:

0.00354

Gnomad OTH exome

AF:

0.00335

GnomAD4 exome

AF:

0.00266

AC:

3870

AN:

1456292

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

1916

AN XY:

724388

show subpopulations

Gnomad4 AFR exome

AF:

0.000424

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.00580

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000590

Gnomad4 FIN exome

AF:

0.00543

Gnomad4 NFE exome

AF:

0.00285

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

AF:

0.00239

AC:

364

AN:

152282

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00509

Gnomad4 NFE

AF:

0.00316

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00292

Hom.:

Bravo

AF:

0.00209

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00268

AC:

ExAC

AF:

0.00255

AC:

310

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00436

EpiControl

AF:

0.00440

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

MAP3K21: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

T;.

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-5.1

D;D

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;.

Vest4

0.87

MVP

0.53

MPC

0.55

ClinPred

0.030

GERP RS

5.3

Varity_R

0.76

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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