rs3743354

Positions:

• chr15-67543173-T-C
• chr15-67543173-T-G

Variant summary

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

The NM_145160.3(MAP2K5):​c.-163T>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 0.112 in 690,032 control chromosomes in the GnomAD database, including 5,501 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 (2124 hom., cov: 31)
  • Exomes 𝑓: 0.10 (3377 hom.)
• Consequence: MAP2K5 NM_145160.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635

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 = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2K5	NM_145160.3	c.-163T>C		5_prime_UTR_variant	1/22	ENST00000178640.10	NP_660143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2K5	ENST00000178640.10	c.-163T>C		5_prime_UTR_variant	1/22	1	NM_145160.3	ENSP00000178640	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22238 AN: 151560 Hom.: 2119 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0656

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0878

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.102 AC: 54973 AN: 538354 Hom.: 3377 Cov.: 7 AF XY: 0.100 AC XY: 28257 AN XY: 281780

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.0874

Gnomad4 ASJ exome AF: 0.0667

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.0944

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.0867

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.147 AC: 22262 AN: 151678 Hom.: 2124 Cov.: 31 AF XY: 0.150 AC XY: 11110 AN XY: 74142

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0656

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.0878

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0559 Hom.: 59

Bravo AF: 0.150

Asia WGS AF: 0.125 AC: 434 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	4.3
DANN	Benign	0.64
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: rs3743354; hg19: chr15-67835511; COSMIC: COSV51618507; COSMIC: COSV51618507;