chr17-21310470-A-G

Variant names:

• chr17-21310470-A-G
• rs9901404
• NM_145109.3:c.775-1672A>G

Variant summary

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

The NM_145109.3(MAP2K3):​c.775-1672A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,098 control chromosomes in the GnomAD database, including 26,942 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 0.58 (26942 hom., cov: 34)
• Consequence: MAP2K3 NM_145109.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717
• Publications: 7 publications found

Genes affected

MAP2K3 (HGNC:6843): (mitogen-activated protein kinase kinase 3) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. It phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. The inhibition of this kinase is involved in the pathogenesis of Yersina pseudotuberculosis. Multiple alternatively spliced transcript variants that encode distinct isoforms have been reported for this gene. [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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K3	NM_145109.3	c.775-1672A>G		intron_variant	Intron 9 of 11	ENST00000342679.9	NP_659731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K3	ENST00000342679.9	c.775-1672A>G		intron_variant	Intron 9 of 11	1	NM_145109.3	ENSP00000345083.4

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88202 AN: 151978 Hom.: 26902 Cov.: 34

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.581 AC: 88299 AN: 152098 Hom.: 26942 Cov.: 34 AF XY: 0.582 AC XY: 43279 AN XY: 74340

African (AFR) AF: 0.776 AC: 32218 AN: 41514

American (AMR) AF: 0.494 AC: 7548 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1771 AN: 3470

East Asian (EAS) AF: 0.559 AC: 2894 AN: 5178

South Asian (SAS) AF: 0.711 AC: 3430 AN: 4824

European-Finnish (FIN) AF: 0.498 AC: 5270 AN: 10576

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.490 AC: 33277 AN: 67950

Other (OTH) AF: 0.575 AC: 1216 AN: 2116

Alfa AF: 0.416 Hom.: 1297

Bravo AF: 0.581

Asia WGS AF: 0.673 AC: 2342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.40
PhyloP100		-0.72
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: rs9901404; hg19: chr17-21213782;