rs12593813

Variant names:

• chr15-67744514-A-G
• rs12593813
• NM_145160.3:c.1075-3717A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_145160.3(MAP2K5):​c.1075-3717A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,206 control chromosomes in the GnomAD database, including 23,614 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (23614 hom., cov: 33)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 47 publications found

Genes affected

MAP2K5 (HGNC:6845): (mitogen-activated protein kinase kinase 5) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been described. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145160.3. 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
	MAP2K5	NM_145160.3	MANE Select	c.1075-3717A>G		intron	N/A	NP_660143.1	Q13163-1
	MAP2K5	NM_002757.4		c.1045-3717A>G		intron	N/A	NP_002748.1	Q13163-2
	MAP2K5	NM_001206804.2		c.967-3717A>G		intron	N/A	NP_001193733.1	Q13163-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K5	ENST00000178640.10	TSL:1 MANE Select	c.1075-3717A>G		intron	N/A	ENSP00000178640.5	Q13163-1
	MAP2K5	ENST00000395476.6	TSL:1	c.1045-3717A>G		intron	N/A	ENSP00000378859.2	Q13163-2
	MAP2K5	ENST00000952141.1		c.1075-3717A>G		intron	N/A	ENSP00000622200.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80388 AN: 152088 Hom.: 23618 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.537

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.528 AC: 80387 AN: 152206 Hom.: 23614 Cov.: 33 AF XY: 0.525 AC XY: 39091 AN XY: 74402

African (AFR) AF: 0.291 AC: 12081 AN: 41554

American (AMR) AF: 0.429 AC: 6559 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1850 AN: 3466

East Asian (EAS) AF: 0.364 AC: 1884 AN: 5176

South Asian (SAS) AF: 0.548 AC: 2645 AN: 4824

European-Finnish (FIN) AF: 0.688 AC: 7280 AN: 10588

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46049 AN: 67992

Other (OTH) AF: 0.534 AC: 1128 AN: 2112

Alfa AF: 0.612 Hom.: 96742

Bravo AF: 0.493

Asia WGS AF: 0.409 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12593813; hg19: chr15-68036852;