17-19381095-G-T

Variant names:

• chr17-19381095-G-T
• rs147296805
• NM_002749.4:c.886G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4 BS2_Supporting

The NM_002749.4(MAPK7):​c.886G>T​(p.Ala296Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: MAPK7 NM_002749.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.20

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28227055).
• BS2: High AC in GnomAdExome4 at 7 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK7	NM_002749.4	c.886G>T	p.Ala296Ser	missense_variant	Exon 4 of 7	ENST00000395604.8	NP_002740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK7	ENST00000395604.8	c.886G>T	p.Ala296Ser	missense_variant	Exon 4 of 7	1	NM_002749.4	ENSP00000378968.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250868 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135674

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461684 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.090	T;.;T;T;T
Eigen	Benign	0.018
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D;D;.;.;D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.31	N;.;N;N;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.070	N;N;N;N;.
REVEL	Benign	0.098
Sift	Benign	0.71	T;T;T;T;.
Sift4G	Benign	0.79	T;T;T;T;T
Polyphen		0.59	P;.;P;P;.
Vest4		0.18
MutPred		0.34		Gain of phosphorylation at A296 (P = 0.0365);.;Gain of phosphorylation at A296 (P = 0.0365);Gain of phosphorylation at A296 (P = 0.0365);.;
MVP		0.55
MPC		0.38
ClinPred		0.41	T
GERP RS		5.0
Varity_R		0.42
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs147296805; hg19: chr17-19284408;