14-70730627-C-G

Position:

• chr14-70730627-C-G

Variant summary

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

The ENST00000554752.7(MAP3K9):​c.3068G>C​(p.Ser1023Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1023C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP3K9 ENST00000554752.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02

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=0.12687144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K9	NM_001284230.2	c.3068G>C	p.Ser1023Thr	missense_variant	12/12	ENST00000554752.7	NP_001271159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K9	ENST00000554752.7	c.3068G>C	p.Ser1023Thr	missense_variant	12/12	1	NM_001284230.2	ENSP00000451612	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jul 25, 2023

The c.3110G>C (p.S1037T) alteration is located in exon 13 (coding exon 13) of the MAP3K9 gene. This alteration results from a G to C substitution at nucleotide position 3110, causing the serine (S) at amino acid position 1037 to be replaced by a threonine (T). 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	0.091
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.0070	T;T;.;T;.;.
Eigen	Benign	-0.0093
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	T;T;T;T;D;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T;T;T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.69	.;N;.;.;.;.
MutationTaster	Benign	0.84	D;D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.38	.;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.43	.;T;T;T;T;T
Sift4G	Benign	0.66	T;T;T;T;T;T
Polyphen		0.0040, 0.018, 0.076, 0.65	.;B;B;B;.;P
Vest4		0.21
MutPred		0.17		.;Gain of glycosylation at S1023 (P = 0.0468);.;.;.;.;
MVP		0.68
MPC		0.94
ClinPred		0.66	D
GERP RS		4.8
Varity_R		0.092
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-71197344;