14-70808865-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001284230.2(MAP3K9):​c.307G>A​(p.Val103Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,600,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MAP3K9
NM_001284230.2 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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-DT (HGNC:53189): (MAP3K9 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28608143).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP3K9NM_001284230.2 linkc.307G>A p.Val103Met missense_variant Exon 1 of 12 ENST00000554752.7 NP_001271159.1 P80192-1Q8NEB1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAP3K9ENST00000554752.7 linkc.307G>A p.Val103Met missense_variant Exon 1 of 12 1 NM_001284230.2 ENSP00000451612.2 P80192-1
MAP3K9ENST00000555993.6 linkc.307G>A p.Val103Met missense_variant Exon 1 of 13 1 ENSP00000451263.2 P80192-4
MAP3K9ENST00000381250.8 linkc.307G>A p.Val103Met missense_variant Exon 1 of 11 5 ENSP00000370649.4 J3KPI6
MAP3K9-DTENST00000697755.1 linkn.55C>T non_coding_transcript_exon_variant Exon 1 of 2

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151798
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000270
AC:
6
AN:
222210
Hom.:
0
AF XY:
0.0000413
AC XY:
5
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:
0.00
Gnomad FIN exome
AF:
0.0000596
Gnomad NFE exome
AF:
0.0000501
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000117
AC:
17
AN:
1448526
Hom.:
0
Cov.:
41
AF XY:
0.0000139
AC XY:
10
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:
0.0000117
Gnomad4 OTH exome
AF:
0.0000501
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151798
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
74140
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000626
Hom.:
0
ExAC
AF:
0.0000332
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.307G>A (p.V103M) 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 307, causing the valine (V) at amino acid position 103 to be replaced by a methionine (M). 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
Pathogenic
0.79
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;.;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Benign
-0.49
T
MutationAssessor
Benign
1.9
L;L;.
PrimateAI
Pathogenic
0.95
D
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.18
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.0060
D;D;D
Polyphen
0.98
D;D;.
Vest4
0.48
MutPred
0.44
Gain of MoRF binding (P = 0.297);Gain of MoRF binding (P = 0.297);Gain of MoRF binding (P = 0.297);
MVP
0.44
MPC
0.51
ClinPred
0.39
T
GERP RS
3.3
Varity_R
0.60
gMVP
0.54

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.

Other links and lift over

dbSNP: rs779167690; hg19: chr14-71275582; API