3-185428594-C-A

Variant names:

• chr3-185428594-C-A
• rs376831918
• NM_004721.5:c.13C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004721.5(MAP3K13):​c.13C>A​(p.Gln5Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,435,412 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. Q5E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MAP3K13 NM_004721.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23580319).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004721.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K13	NM_004721.5	MANE Select	c.13C>A	p.Gln5Lys	missense	Exon 2 of 14	NP_004712.1	O43283-1
	MAP3K13	NM_001242314.2		c.13C>A	p.Gln5Lys	missense	Exon 3 of 15	NP_001229243.1	O43283-1
	MAP3K13	NM_001242317.2		c.39-14851C>A		intron	N/A	NP_001229246.1	O43283-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K13	ENST00000265026.8	TSL:1 MANE Select	c.13C>A	p.Gln5Lys	missense	Exon 2 of 14	ENSP00000265026.3	O43283-1
	MAP3K13	ENST00000424227.5	TSL:1	c.13C>A	p.Gln5Lys	missense	Exon 3 of 15	ENSP00000399910.1	O43283-1
	MAP3K13	ENST00000433092.5	TSL:1	n.13C>A		non_coding_transcript_exon	Exon 2 of 7	ENSP00000389798.1	O43283-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1435412 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 710514

African (AFR) AF: 0.00 AC: 0 AN: 32684

American (AMR) AF: 0.00 AC: 0 AN: 42030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24668

East Asian (EAS) AF: 0.00 AC: 0 AN: 39330

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52678

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5472

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096552

Other (OTH) AF: 0.00 AC: 0 AN: 59064

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.030
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.0	L
PhyloP100		5.8
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.16
Sift	Benign	0.047	D
Sift4G	Benign	0.29	T
Polyphen		0.28	B
Vest4		0.55
MutPred		0.12		Gain of ubiquitination at C5 (P = 0.0042)
MVP		0.77
MPC		0.23
ClinPred		0.77	D
GERP RS		5.6
Varity_R		0.17
gMVP		0.51
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs376831918; hg19: chr3-185146382;