NM_002749.4:c.-121T>A

Variant names:

• chr17-19378515-T-A
• rs2233072
• NM_002749.4:c.-121T>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.-121T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000318 in 943,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: MAPK7 NM_002749.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK7	NM_002749.4	c.-121T>A		5_prime_UTR_variant	Exon 1 of 7	ENST00000395604.8	NP_002740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK7	ENST00000395604.8	c.-121T>A		5_prime_UTR_variant	Exon 1 of 7	1	NM_002749.4	ENSP00000378968.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000318 AC: 3 AN: 943124 Hom.: 0 Cov.: 44 AF XY: 0.00000676 AC XY: 3 AN XY: 443726

African (AFR) AF: 0.00 AC: 0 AN: 18316

American (AMR) AF: 0.00 AC: 0 AN: 5360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8248

East Asian (EAS) AF: 0.00 AC: 0 AN: 8682

South Asian (SAS) AF: 0.00 AC: 0 AN: 33848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2100

European-Non Finnish (NFE) AF: 0.00000363 AC: 3 AN: 827090

Other (OTH) AF: 0.00 AC: 0 AN: 33594

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.5
DANN	Benign	0.68
PhyloP100		0.20
PromoterAI		0.015	Neutral

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: rs2233072; hg19: chr17-19281828;