chr14-70732587-C-A

Position:

• chr14-70732587-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000554752.7(MAP3K9):​c.2782G>T​(p.Ala928Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MAP3K9 ENST00000554752.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.766

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]

ACMG classification

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=0.07778308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K9	NM_001284230.2	c.2782G>T	p.Ala928Ser	missense_variant	11/12	ENST00000554752.7	NP_001271159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K9	ENST00000554752.7	c.2782G>T	p.Ala928Ser	missense_variant	11/12	1	NM_001284230.2	ENSP00000451612	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452512 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.2824G>T (p.A942S) alteration is located in exon 12 (coding exon 12) of the MAP3K9 gene. This alteration results from a G to T substitution at nucleotide position 2824, causing the alanine (A) at amino acid position 942 to be replaced by a serine (S). 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	0.077
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	9.4
DANN	Benign	0.51
DEOGEN2	Benign	0.0038	T;T;.;T;.;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.76	T;T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.078	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	.;N;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.040	.;N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.60	.;T;T;T;T;T
Sift4G	Benign	0.78	T;T;T;T;T;T
Polyphen		0.0010, 0.0030, 0.089, 0.050	.;B;B;B;.;B
Vest4		0.16
MutPred		0.12		.;Gain of phosphorylation at A928 (P = 0.0039);.;.;.;.;
MVP		0.45
MPC		0.27
ClinPred		0.13	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.093
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-71199304;