Genetic Variant NM_145160.3:c.-163T>C (chr15-67543173-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.635

Publications

11 publications found

Variant links:

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]

MAP2K5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP2K5	NM_145160.3 link	c.-163T>C		5_prime_UTR_variant	Exon 1 of 22	ENST00000178640.10	NP_660143.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
MAP2K5	ENST00000178640.10 link	c.-163T>C	5_prime_UTR_variant	Exon 1 of 22	1	NM_145160.3	ENSP00000178640.5
MAP2K5	ENST00000395476.6 link	c.-163T>C	upstream_gene_variant		1		ENSP00000378859.2
MAP2K5	ENST00000560591.5 link	n.-90T>C	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22238

AN:

151560

Hom.:

2119

Cov.:

show subpopulations

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.:

AF XY:

0.100

AC XY:

28257

AN XY:

281780

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2306

4613

6919

9226

11532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

482

964

1446

1928

2410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.147

AC:

22262

AN:

151678

Hom.:

2124

Cov.:

AF XY:

0.150

AC XY:

11110

AN XY:

74142

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0878

AC:

5959

AN:

67882

Other (OTH)

AF:

0.131

AC:

276

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

907

1814

2721

3628

4535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0643

Hom.:

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

(source)

DANN

Benign

0.64

PhyloP100

-0.64

PromoterAI

-0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over