17-19379914-G-A

Variant names:

• chr17-19379914-G-A
• rs753677940
• NM_002749.4:c.365G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002749.4(MAPK7):​c.365G>A​(p.Arg122Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. R122M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MAPK7 NM_002749.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062173575).

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.365G>A	p.Arg122Lys	missense	Exon 3 of 7	NP_002740.2
	MAPK7	NM_139033.3		c.365G>A	p.Arg122Lys	missense	Exon 3 of 7	NP_620602.2	Q13164-1
	MAPK7	NM_139034.3		c.365G>A	p.Arg122Lys	missense	Exon 3 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.365G>A	p.Arg122Lys	missense	Exon 3 of 7	ENSP00000378968.3	Q13164-1
	MAPK7	ENST00000308406.9	TSL:1	c.365G>A	p.Arg122Lys	missense	Exon 3 of 7	ENSP00000311005.5	Q13164-1
	MAPK7	ENST00000395602.8	TSL:1	c.365G>A	p.Arg122Lys	missense	Exon 3 of 7	ENSP00000378966.4	Q13164-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251410 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727232

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

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.61	N
PhyloP100		2.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.032
Sift	Benign	0.88	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.095
MutPred		0.32		Gain of ubiquitination at R122 (P = 0.0219)
MVP		0.51
MPC		0.43
ClinPred		0.057	T
GERP RS		1.0
Varity_R		0.23
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs753677940; hg19: chr17-19283227;