17-19378986-C-G

Variant names:

• chr17-19378986-C-G
• rs1235673576
• NM_002749.4:c.86C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_002749.4(MAPK7):​c.86C>G​(p.Ala29Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000823 in 1,458,788 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: MAPK7 NM_002749.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.871
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.055873126).
• BS2: High AC in GnomAdExome4 at 12 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.86C>G	p.Ala29Gly	missense_variant	Exon 2 of 7	ENST00000395604.8	NP_002740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK7	ENST00000395604.8	c.86C>G	p.Ala29Gly	missense_variant	Exon 2 of 7	1	NM_002749.4	ENSP00000378968.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000411 AC: 1 AN: 243538 AF XY: 0.00000757

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: 0.00000910

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000823 AC: 12 AN: 1458788 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 725428

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 85592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1110834

Other (OTH) AF: 0.00 AC: 0 AN: 60262

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.86C>G (p.A29G) alteration is located in exon 2 (coding exon 1) of the MAPK7 gene. This alteration results from a C to G substitution at nucleotide position 86, causing the alanine (A) at amino acid position 29 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T;T;T;.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.56	T;.;T;T;.;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.056	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;.;.;L;.
PhyloP100		0.87
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.12	N;N;.;N;N;.
REVEL	Benign	0.065
Sift	Benign	0.11	T;T;.;T;T;.
Sift4G	Benign	0.45	T;T;T;T;T;T
Polyphen		0.0	B;B;.;.;B;.
Vest4		0.26
MutPred		0.22		Gain of catalytic residue at A29 (P = 0.029);Gain of catalytic residue at A29 (P = 0.029);Gain of catalytic residue at A29 (P = 0.029);Gain of catalytic residue at A29 (P = 0.029);Gain of catalytic residue at A29 (P = 0.029);Gain of catalytic residue at A29 (P = 0.029);
MVP		0.42
MPC		0.42
ClinPred		0.047	T
GERP RS		1.2
PromoterAI		-0.029	Neutral
Varity_R		0.038
gMVP		0.17
Mutation Taster		=79/21	polymorphism

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

dbSNP: rs1235673576; hg19: chr17-19282299;