rs3743353

Variant names:

• chr15-67543032-T-C
• rs3743353
• NM_145160.3:c.-304T>C

Variant summary

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

The NM_145160.3(MAP2K5):​c.-304T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 413,610 control chromosomes in the GnomAD database, including 3,864 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 0.15 (2137 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1727 hom.)
• Consequence: MAP2K5 NM_145160.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545

Genes affected

MAP2K5 (HGNC:6845): (mitogen-activated protein kinase kinase 5) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been described. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.-304T>C		5_prime_UTR_variant	Exon 1 of 22	ENST00000178640.10	NP_660143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640	c.-304T>C		5_prime_UTR_variant	Exon 1 of 22	1	NM_145160.3	ENSP00000178640.5
MAP2K5	ENST00000560591.5	n.-231T>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22313 AN: 152010 Hom.: 2133 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.101 AC: 26525 AN: 261482 Hom.: 1727 Cov.: 0 AF XY: 0.0999 AC XY: 13691 AN XY: 137026

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.0912

Gnomad4 ASJ exome AF: 0.0657

Gnomad4 EAS exome AF: 0.192

Gnomad4 SAS exome AF: 0.0931

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.0842

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.147 AC: 22333 AN: 152128 Hom.: 2137 Cov.: 32 AF XY: 0.150 AC XY: 11148 AN XY: 74362

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.0877

Gnomad4 OTH AF: 0.131

Alfa AF: 0.111 Hom.: 288

Bravo AF: 0.150

Asia WGS AF: 0.127 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	10
DANN	Benign	0.78
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: rs3743353; hg19: chr15-67835370;