NM_002749.4:c.466C>A

Variant names:

• chr17-19380675-C-A
• NM_002749.4:c.466C>A

Variant summary

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

The NM_002749.4(MAPK7):​c.466C>A​(p.Leu156Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAPK7 NM_002749.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0760
• Publications: 0 publications found

Genes affected

MAPK7 (HGNC:6880): (mitogen-activated protein kinase 7) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the downstream signaling processes of various receptor molecules including receptor type kinases, and G protein-coupled receptors. In response to extracelluar signals, this kinase translocates to cell nucleus, where it regulates gene expression by phosphorylating, and activating different transcription factors. Four alternatively spliced transcript variants of this gene encoding two distinct isoforms have been reported. [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=0.21843281).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002749.4. 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
	MAPK7	NM_002749.4	MANE Select	c.466C>A	p.Leu156Met	missense	Exon 4 of 7	NP_002740.2
	MAPK7	NM_139033.3		c.466C>A	p.Leu156Met	missense	Exon 4 of 7	NP_620602.2	Q13164-1
	MAPK7	NM_139034.3		c.466C>A	p.Leu156Met	missense	Exon 4 of 7	NP_620603.2	Q13164-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK7	ENST00000395604.8	TSL:1 MANE Select	c.466C>A	p.Leu156Met	missense	Exon 4 of 7	ENSP00000378968.3	Q13164-1
	MAPK7	ENST00000308406.9	TSL:1	c.466C>A	p.Leu156Met	missense	Exon 4 of 7	ENSP00000311005.5	Q13164-1
	MAPK7	ENST00000395602.8	TSL:1	c.466C>A	p.Leu156Met	missense	Exon 4 of 7	ENSP00000378966.4	Q13164-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461738 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727148

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111900

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

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	0.18
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.076
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.093
Sift	Benign	0.069	T
Sift4G	Uncertain	0.060	T
Polyphen		0.62	P
Vest4		0.40
MutPred		0.41		Gain of disorder (P = 0.1149)
MVP		0.66
MPC		0.44
ClinPred		0.26	T
GERP RS		2.5
Varity_R		0.10
gMVP		0.17

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

hg19: chr17-19283988;