NM_145160.3:c.*355C>T

Variant names:

• chr15-67807105-C-T
• rs41305272
• NM_145160.3:c.*355C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_145160.3(MAP2K5):​c.*355C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0319 in 572,126 control chromosomes in the GnomAD database, including 372 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 0.024 (58 hom., cov: 33)
  • Exomes 𝑓: 0.035 (314 hom.)
• Consequence: MAP2K5 NM_145160.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 12 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=-0.51).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0238 (3625/152330) while in subpopulation NFE AF = 0.0401 (2725/68022). AF 95% confidence interval is 0.0388. There are 58 homozygotes in GnomAd4. There are 1651 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3625 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K5	NM_145160.3	MANE Select	c.*355C>T		3_prime_UTR	Exon 22 of 22	NP_660143.1	Q13163-1
	MAP2K5	NM_002757.4		c.*355C>T		3_prime_UTR	Exon 21 of 21	NP_002748.1	Q13163-2
	MAP2K5	NM_001206804.2		c.*355C>T		3_prime_UTR	Exon 22 of 22	NP_001193733.1	Q13163-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K5	ENST00000178640.10	TSL:1 MANE Select	c.*355C>T		3_prime_UTR	Exon 22 of 22	ENSP00000178640.5	Q13163-1
	MAP2K5	ENST00000395476.6	TSL:1	c.*355C>T		3_prime_UTR	Exon 21 of 21	ENSP00000378859.2	Q13163-2
	MAP2K5	ENST00000879775.1		c.*355C>T		splice_region	Exon 23 of 23	ENSP00000549834.1

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3627 AN: 152212 Hom.: 59 Cov.: 33

Gnomad AFR AF: 0.00736

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0401

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.0348 AC: 14610 AN: 419796 Hom.: 314 Cov.: 7 AF XY: 0.0333 AC XY: 7119 AN XY: 213960

African (AFR) AF: 0.00507 AC: 51 AN: 10060

American (AMR) AF: 0.0168 AC: 196 AN: 11654

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 129 AN: 7196

East Asian (EAS) AF: 0.00 AC: 0 AN: 11514

South Asian (SAS) AF: 0.00822 AC: 369 AN: 44896

European-Finnish (FIN) AF: 0.0169 AC: 181 AN: 10720

Middle Eastern (MID) AF: 0.0407 AC: 50 AN: 1228

European-Non Finnish (NFE) AF: 0.0429 AC: 13034 AN: 304170

Other (OTH) AF: 0.0327 AC: 600 AN: 18358

GnomAD4 genome AF: 0.0238 AC: 3625 AN: 152330 Hom.: 58 Cov.: 33 AF XY: 0.0222 AC XY: 1651 AN XY: 74490

African (AFR) AF: 0.00734 AC: 305 AN: 41568

American (AMR) AF: 0.0165 AC: 252 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4830

European-Finnish (FIN) AF: 0.0108 AC: 115 AN: 10622

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0401 AC: 2725 AN: 68022

Other (OTH) AF: 0.0175 AC: 37 AN: 2116

Alfa AF: 0.0320 Hom.: 44

Bravo AF: 0.0236

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.5
DANN	Benign	0.78
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41305272;

hg19: chr15-68099443;