Variant chr14-70809096-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000554752.7(MAP3K9):c.76G>A(p.Gly26Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,246,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

MAP3K9
ENST00000554752.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.183

Variant links:

Genes affected

MAP3K9 (HGNC:6861): (mitogen-activated protein kinase kinase kinase 9) Enables protein serine/threonine kinase activity. Involved in protein autophosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

MAP3K9 links:

MAP3K9-DT (HGNC:):

MAP3K9-DT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18797725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K9	NM_001284230.2 linkuse as main transcript	c.76G>A	p.Gly26Arg	missense_variant	1/12	ENST00000554752.7	NP_001271159.1	P80192-1Q8NEB1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAP3K9	ENST00000554752.7 linkuse as main transcript	c.76G>A	p.Gly26Arg	missense_variant	1/12	1	NM_001284230.2	ENSP00000451612.2	P80192-1
MAP3K9	ENST00000555993.6 linkuse as main transcript	c.76G>A	p.Gly26Arg	missense_variant	1/13	1		ENSP00000451263.2	P80192-4
MAP3K9	ENST00000381250.8 linkuse as main transcript	c.76G>A	p.Gly26Arg	missense_variant	1/11	5		ENSP00000370649.4	J3KPI6
MAP3K9-DT	ENST00000697755.1 linkuse as main transcript	n.286C>T		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000150

AC:

AN:

19946

Hom.:

AF XY:

0.000193

AC XY:

AN XY:

10386

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000127

Gnomad OTH exome

AF:

0.00141

GnomAD4 exome

AF:

0.0000168

AC:

AN:

1246834

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

605328

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000678

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000177

Gnomad4 OTH exome

AF:

0.0000193

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Aug 13, 2021

The c.76G>A (p.G26R) alteration is located in exon 1 (coding exon 1) of the MAP3K9 gene. This alteration results from a G to A substitution at nucleotide position 76, causing the glycine (G) at amino acid position 26 to be replaced by an arginine (R). 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

0.21

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

T;.;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.83

T;D;T

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.0

N;N;.

MutationTaster

Benign

0.58

N;N;N

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.78

N;N;N

REVEL

Benign

0.11

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.13

T;T;T

Polyphen

0.0020

B;B;.

Vest4

0.18

MutPred

0.22

Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);

MVP

0.48

MPC

0.34

ClinPred

0.12

GERP RS

3.1

Varity_R

0.15

gMVP

0.28

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