Variant 2-134983797-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_025052.5(MAP3K19):c.3101A>G(p.Asp1034Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,601,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

MAP3K19
NM_025052.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.800

Variant links:

Genes affected

MAP3K19 (HGNC:26249): (mitogen-activated protein kinase kinase kinase 19) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

MAP3K19 links:

MAP3K19 (HGNC:):

MAP3K19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029063582).

BS2

High AC in GnomAd4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K19	NM_025052.5 linkuse as main transcript	c.3101A>G	p.Asp1034Gly	missense_variant	11/13	ENST00000392915.7	NP_079328.3	Q56UN5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K19	ENST00000392915.7 linkuse as main transcript	c.3101A>G	p.Asp1034Gly	missense_variant	11/13	5	NM_025052.5	ENSP00000376647.2		Q56UN5-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000213

AC:

AN:

239018

Hom.:

AF XY:

0.000216

AC XY:

AN XY:

129510

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000954

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000355

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000363

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.000170

AC:

247

AN:

1449266

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

122

AN XY:

721152

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00105

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000166

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000173

Gnomad4 OTH exome

AF:

0.000217

GnomAD4 genome

AF:

0.000164

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000253

Hom.:

Bravo

AF:

0.000102

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000280

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.3101A>G (p.D1034G) alteration is located in exon 8 (coding exon 8) of the MAP3K19 gene. This alteration results from a A to G substitution at nucleotide position 3101, causing the aspartic acid (D) at amino acid position 1034 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0030

T;T;.;.;.;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.73

.;T;T;T;T;T

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.029

T;T;T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.3

L;L;.;.;.;.

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.0

.;D;D;D;N;D

REVEL

Benign

0.076

Sift

Benign

0.071

.;T;T;T;T;T

Sift4G

Benign

0.095

.;T;T;T;T;T

Polyphen

0.022

B;B;B;B;B;.

Vest4

0.27, 0.25, 0.18, 0.35

MVP

0.76

MPC

0.16

ClinPred

0.023

GERP RS

4.2

Varity_R

0.17

gMVP

0.42

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

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