3-185482395-A-T

Variant names:

• chr3-185482395-A-T
• NM_004721.5:c.2840A>T

Variant summary

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

The NM_004721.5(MAP3K13):​c.2840A>T​(p.Asp947Val) 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. 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. D947H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP3K13 NM_004721.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.94

Genes affected

MAP3K13 (HGNC:6852): (mitogen-activated protein kinase kinase kinase 13) The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase contains a dual leucine-zipper motif, and has been shown to form dimers/oligomers through its leucine-zipper motif. This kinase can phosphorylate and activate MAPK8/JNK, MAP2K7/MKK7, which suggests a role in the JNK signaling pathway. [provided by RefSeq, Jul 2008]

TMEM41A (HGNC:30544): (transmembrane protein 41A) Predicted to be integral component of membrane. [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=0.19284263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K13	NM_004721.5	c.2840A>T	p.Asp947Val	missense_variant	Exon 14 of 14	ENST00000265026.8	NP_004712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K13	ENST00000265026.8	c.2840A>T	p.Asp947Val	missense_variant	Exon 14 of 14	1	NM_004721.5	ENSP00000265026.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2840A>T (p.D947V) alteration is located in exon 14 (coding exon 13) of the MAP3K13 gene. This alteration results from a A to T substitution at nucleotide position 2840, causing the aspartic acid (D) at amino acid position 947 to be replaced by a valine (V). 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	0.20
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	.;T;.;T
Eigen	Benign	0.086
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;.;D;D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.55	.;N;.;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.3	N;D;N;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.44	B;B;B;B
Vest4		0.27
MutPred		0.26		.;Gain of glycosylation at S945 (P = 0.0155);.;Gain of glycosylation at S945 (P = 0.0155);
MVP		0.68
MPC		0.47
ClinPred		0.77	D
GERP RS		4.7
Varity_R		0.22
gMVP		0.21

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: chr3-185200183;