dbSNP rs779167690: MAP3K9:p.Val103Leu (chr14-70808865-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001284230.2(MAP3K9):c.307G>C(p.Val103Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V103M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MAP3K9
NM_001284230.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.34

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:53189): (MAP3K9 divergent transcript)

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=0.15523118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K9	NM_001284230.2 link	c.307G>C	p.Val103Leu	missense_variant	Exon 1 of 12	ENST00000554752.7	NP_001271159.1	P80192-1Q8NEB1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAP3K9	ENST00000554752.7 link	c.307G>C	p.Val103Leu	missense_variant	Exon 1 of 12	1	NM_001284230.2	ENSP00000451612.2	P80192-1
MAP3K9	ENST00000555993.6 link	c.307G>C	p.Val103Leu	missense_variant	Exon 1 of 13	1		ENSP00000451263.2	P80192-4
MAP3K9	ENST00000381250.8 link	c.307G>C	p.Val103Leu	missense_variant	Exon 1 of 11	5		ENSP00000370649.4	J3KPI6
MAP3K9-DT	ENST00000697755.1 link	n.55C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000450

AC:

AN:

222210

Hom.:

AF XY:

0.00

AC XY:

AN XY:

121178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000356

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1448526

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719740

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000830

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

L;L;.

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.012

B;B;.

Vest4

0.25

MutPred

0.59

Loss of MoRF binding (P = 0.2969);Loss of MoRF binding (P = 0.2969);Loss of MoRF binding (P = 0.2969);

MVP

0.42

MPC

0.29

ClinPred

0.28

GERP RS

3.3

Varity_R

0.39

gMVP

0.52

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over