NM_145160.3:c.260C>T

Variant names:

• chr15-67580761-C-T
• rs781247733
• NM_145160.3:c.260C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_145160.3(MAP2K5):​c.260C>T​(p.Ser87Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000173 in 1,445,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: MAP2K5 NM_145160.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 25 AD gene.

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.260C>T	p.Ser87Phe	missense	Exon 4 of 22	NP_660143.1	Q13163-1
	MAP2K5	NM_002757.4		c.260C>T	p.Ser87Phe	missense	Exon 4 of 21	NP_002748.1	Q13163-2
	MAP2K5	NM_001206804.2		c.152C>T	p.Ser51Phe	missense	Exon 4 of 22	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.260C>T	p.Ser87Phe	missense	Exon 4 of 22	ENSP00000178640.5	Q13163-1
	MAP2K5	ENST00000395476.6	TSL:1	c.260C>T	p.Ser87Phe	missense	Exon 4 of 21	ENSP00000378859.2	Q13163-2
	MAP2K5	ENST00000952141.1		c.260C>T	p.Ser87Phe	missense	Exon 4 of 24	ENSP00000622200.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000758 AC: 19 AN: 250628 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000173 AC: 25 AN: 1445368 Hom.: 0 Cov.: 27 AF XY: 0.0000111 AC XY: 8 AN XY: 720146

African (AFR) AF: 0.00 AC: 0 AN: 33172

American (AMR) AF: 0.000470 AC: 21 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.00 AC: 0 AN: 85888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5530

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1098240

Other (OTH) AF: 0.0000167 AC: 1 AN: 59798

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000261 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.20
Sift	Benign	0.042	D
Sift4G	Benign	0.14	T
Polyphen		0.42	B
Vest4		0.46
MutPred		0.87		Loss of disorder (P = 0.1261)
MVP		0.60
MPC		0.32
ClinPred		0.13	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.36
Mutation Taster		=38/62	disease causing

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: rs781247733; hg19: chr15-67873099; COSMIC: COSV105044902; COSMIC: COSV105044902;