16-30114479-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

ENSG00000300821 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002746.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK3	NM_002746.3	MANE Select	c.*262C>T		3_prime_UTR	Exon 9 of 9	NP_002737.2
	MAPK3	NM_001109891.2		c.*262C>T		3_prime_UTR	Exon 8 of 8	NP_001103361.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK3	ENST00000263025.9	TSL:1 MANE Select	c.*262C>T		3_prime_UTR	Exon 9 of 9	ENSP00000263025.4
	MAPK3	ENST00000484663.5	TSL:1	c.*262C>T		3_prime_UTR	Exon 8 of 8	ENSP00000432742.1
	MAPK3	ENST00000466521.5	TSL:5	n.*468C>T		non_coding_transcript_exon	Exon 9 of 9	ENSP00000433746.1

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

African (AFR) AF: 0.667 AC: 4 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 14

South Asian (SAS) AF: 0.00 AC: 0 AN: 8

European-Finnish (FIN) AF: 0.0486 AC: 21 AN: 432

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.114 AC: 30 AN: 264

Other (OTH) AF: 0.00 AC: 0 AN: 18

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

African (AFR) AF: 0.156 AC: 6179 AN: 39616

American (AMR) AF: 0.0832 AC: 1250 AN: 15022

Ashkenazi Jewish (ASJ) AF: 0.0788 AC: 270 AN: 3428

East Asian (EAS) AF: 0.00167 AC: 8 AN: 4804

South Asian (SAS) AF: 0.0321 AC: 144 AN: 4492

European-Finnish (FIN) AF: 0.0382 AC: 376 AN: 9834

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.0780 AC: 5213 AN: 66844

Other (OTH) AF: 0.100 AC: 206 AN: 2058

Alfa AF: 0.0885 Hom.: 935

Bravo AF: 0.0998

Asia WGS AF: 0.0260 AC: 90 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.63
PhyloP100		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs7698; hg19: chr16-30125800;