rs7698

Variant names:

• chr16-30114479-G-A
• rs7698
• NM_002746.3:c.*262C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002746.3(MAPK3):​c.*262C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 148,036 control chromosomes in the GnomAD database, including 805 homozygotes. 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: 𝑓 0.093 (800 hom., cov: 31)
  • Exomes 𝑓: 0.075 (5 hom.)
• Consequence: MAPK3 NM_002746.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695

Genes affected

MAPK3 (HGNC:6877): (mitogen-activated protein kinase 3) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK3	NM_002746.3	c.*262C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000263025.9	NP_002737.2
MAPK3	NM_001109891.2	c.*262C>T		3_prime_UTR_variant	Exon 8 of 8		NP_001103361.1
MAPK3	XR_243293.2	n.1464C>T		non_coding_transcript_exon_variant	Exon 10 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK3	ENST00000263025	c.*262C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_002746.3	ENSP00000263025.4

Frequencies

GnomAD3 genomes AF: 0.0935 AC: 13754 AN: 147166 Hom.: 798 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0913

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.0788

Gnomad EAS AF: 0.00166

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0382

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0749 AC: 56 AN: 748 Hom.: 5 Cov.: 0 AF XY: 0.0813 AC XY: 41 AN XY: 504

Gnomad4 AFR exome AF: 0.667

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0486

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0934 AC: 13763 AN: 147288 Hom.: 800 Cov.: 31 AF XY: 0.0896 AC XY: 6448 AN XY: 71938

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0832

Gnomad4 ASJ AF: 0.0788

Gnomad4 EAS AF: 0.00167

Gnomad4 SAS AF: 0.0321

Gnomad4 FIN AF: 0.0382

Gnomad4 NFE AF: 0.0780

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0888 Hom.: 585

Bravo AF: 0.0998

Asia WGS AF: 0.0260 AC: 90 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7698; hg19: chr16-30125800;