rs78564187

Variant names:

• chr16-30120456-G-A
• rs78564187
• NM_002746.3:c.353+1368C>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.353+1368C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,104 control chromosomes in the GnomAD database, including 1,083 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 0.10 (1083 hom., cov: 31)
• Consequence: MAPK3 NM_002746.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 6 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]

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 (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK3	NM_002746.3	c.353+1368C>T		intron_variant	Intron 2 of 8	ENST00000263025.9	NP_002737.2
MAPK3	NM_001040056.3	c.353+1368C>T		intron_variant	Intron 2 of 6		NP_001035145.1
MAPK3	NM_001109891.2	c.353+1368C>T		intron_variant	Intron 2 of 7		NP_001103361.1
MAPK3	XR_243293.2	n.364+1368C>T		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK3	ENST00000263025.9	c.353+1368C>T		intron_variant	Intron 2 of 8	1	NM_002746.3	ENSP00000263025.4

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15544 AN: 151986 Hom.: 1080 Cov.: 31

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.0629

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0364

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.104

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15555 AN: 152104 Hom.: 1083 Cov.: 31 AF XY: 0.0987 AC XY: 7340 AN XY: 74346

African (AFR) AF: 0.191 AC: 7934 AN: 41456

American (AMR) AF: 0.0866 AC: 1322 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 218 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5168

South Asian (SAS) AF: 0.0293 AC: 141 AN: 4820

European-Finnish (FIN) AF: 0.0364 AC: 386 AN: 10610

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0766 AC: 5208 AN: 67990

Other (OTH) AF: 0.103 AC: 217 AN: 2114

Alfa AF: 0.0840 Hom.: 520

Bravo AF: 0.114

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.46
DANN	Benign	0.41
PhyloP100		-1.0
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: rs78564187; hg19: chr16-30131777;