17-19380859-T-C

Variant names:

• chr17-19380859-T-C
• NM_002749.4:c.650T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002749.4(MAPK7):​c.650T>C​(p.Phe217Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAPK7 NM_002749.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.846

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.650T>C	p.Phe217Ser	missense	Exon 4 of 7	NP_002740.2
	MAPK7	NM_139033.3		c.650T>C	p.Phe217Ser	missense	Exon 4 of 7	NP_620602.2	Q13164-1
	MAPK7	NM_139034.3		c.650T>C	p.Phe217Ser	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.650T>C	p.Phe217Ser	missense	Exon 4 of 7	ENSP00000378968.3	Q13164-1
	MAPK7	ENST00000308406.9	TSL:1	c.650T>C	p.Phe217Ser	missense	Exon 4 of 7	ENSP00000311005.5	Q13164-1
	MAPK7	ENST00000395602.8	TSL:1	c.650T>C	p.Phe217Ser	missense	Exon 4 of 7	ENSP00000378966.4	Q13164-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.095	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.80	N
PhyloP100		7.9
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.65		Gain of disorder (P = 0.0011)
MVP		0.80
MPC		0.75
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.98
gMVP		0.84

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

hg19: chr17-19284172;