15-67543173-T-C

Variant names:

• chr15-67543173-T-C
• rs3743354
• NM_145160.3:c.-163T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145160.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K5	NM_145160.3	MANE Select	c.-163T>C		5_prime_UTR	Exon 1 of 22	NP_660143.1
	MAP2K5	NM_002757.4		c.-163T>C		5_prime_UTR	Exon 1 of 21	NP_002748.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K5	ENST00000178640.10	TSL:1 MANE Select	c.-163T>C		5_prime_UTR	Exon 1 of 22	ENSP00000178640.5
	MAP2K5	ENST00000395476.6	TSL:1	c.-163T>C		upstream_gene	N/A	ENSP00000378859.2
	MAP2K5	ENST00000560591.5	TSL:3	n.-90T>C		upstream_gene	N/A

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

African (AFR) AF: 0.252 AC: 3658 AN: 14504

American (AMR) AF: 0.0874 AC: 1994 AN: 22808

Ashkenazi Jewish (ASJ) AF: 0.0667 AC: 965 AN: 14466

East Asian (EAS) AF: 0.195 AC: 6145 AN: 31582

South Asian (SAS) AF: 0.0944 AC: 4673 AN: 49526

European-Finnish (FIN) AF: 0.136 AC: 4730 AN: 34898

Middle Eastern (MID) AF: 0.0810 AC: 175 AN: 2160

European-Non Finnish (NFE) AF: 0.0867 AC: 29448 AN: 339668

Other (OTH) AF: 0.111 AC: 3185 AN: 28742

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

African (AFR) AF: 0.261 AC: 10789 AN: 41328

American (AMR) AF: 0.122 AC: 1860 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0656 AC: 227 AN: 3462

East Asian (EAS) AF: 0.202 AC: 1030 AN: 5100

South Asian (SAS) AF: 0.104 AC: 498 AN: 4774

European-Finnish (FIN) AF: 0.146 AC: 1539 AN: 10572

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0878 AC: 5959 AN: 67882

Other (OTH) AF: 0.131 AC: 276 AN: 2110

Alfa AF: 0.0643 Hom.: 78

Bravo AF: 0.150

Asia WGS AF: 0.125 AC: 434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.64
PhyloP100		-0.64
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs3743354; hg19: chr15-67835511; COSMIC: COSV51618507; COSMIC: COSV51618507;