rs3810608

Variant names:

• chr22-21758505-G-A
• rs3810608
• ENST00000962868.1:c.*388C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000962868.1(MAPK1):​c.*388C>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 0.175 in 152,214 control chromosomes in the GnomAD database, including 2,719 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 0.18 (2719 hom., cov: 31)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: MAPK1 ENST00000962868.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.05
• Publications: 9 publications found

Genes affected

MAPK1 (HGNC:6871): (mitogen-activated protein kinase 1) This gene encodes a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), 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. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. One study also suggests that this protein acts as a transcriptional repressor independent of its kinase activity. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene. [provided by RefSeq, Jan 2014]

MAPK1 Gene-Disease associations (from GenCC):

• Noonan syndrome 13

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000962868.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK1	ENST00000962868.1		c.*388C>T		3_prime_UTR	Exon 9 of 9	ENSP00000632927.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26625 AN: 151904 Hom.: 2715 Cov.: 31

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.0990

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.115 AC: 22 AN: 192 Hom.: 0 Cov.: 0 AF XY: 0.127 AC XY: 17 AN XY: 134

African (AFR) AF: 0.00 AC: 0 AN: 8

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

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.120 AC: 6 AN: 50

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

European-Non Finnish (NFE) AF: 0.110 AC: 13 AN: 118

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.175 AC: 26630 AN: 152022 Hom.: 2719 Cov.: 31 AF XY: 0.172 AC XY: 12786 AN XY: 74304

African (AFR) AF: 0.0837 AC: 3471 AN: 41486

American (AMR) AF: 0.189 AC: 2881 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 910 AN: 3468

East Asian (EAS) AF: 0.0993 AC: 514 AN: 5178

South Asian (SAS) AF: 0.0998 AC: 481 AN: 4818

European-Finnish (FIN) AF: 0.171 AC: 1809 AN: 10564

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15859 AN: 67922

Other (OTH) AF: 0.203 AC: 428 AN: 2106

Alfa AF: 0.191 Hom.: 471

Bravo AF: 0.171

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.60
PhyloP100		-3.0
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: rs3810608; hg19: chr22-22112794; COSMIC: COSV53189787;