Genetic Variant MAP3K15:c.2934-37G>A (chrX-19372864-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001001671.4(MAP3K15):c.2934-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 1,176,859 control chromosomes in the GnomAD database, including 2,769 homozygotes. There are 17,528 hemizygotes in GnomAD. 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 0.11 ( 1172 hom., 3211 hem., cov: 21)

Exomes 𝑓: 0.039 ( 1597 hom. 14317 hem. )

Consequence

MAP3K15
NM_001001671.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

Publications

1 publications found

Variant links:

Genes affected

MAP3K15 (HGNC:31689): (mitogen-activated protein kinase kinase kinase 15) The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAPK) family. These family members function in a protein kinase signal transduction cascade, where an activated MAPK kinase kinase (MAP3K) phosphorylates and activates a specific MAPK kinase (MAP2K), which then activates a specific MAPK. This MAP3K protein plays an essential role in apoptotic cell death triggered by cellular stresses. [provided by RefSeq, Jul 2010]

MAP3K15 links:

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new If you want to explore the variant's impact on the transcript NM_001001671.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001671.4. 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
	MAP3K15	NM_001001671.4	MANE Select	c.2934-37G>A		intron	N/A	NP_001001671.3	Q6ZN16-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAP3K15	ENST00000338883.9	TSL:5 MANE Select	c.2934-37G>A	intron	N/A	ENSP00000345629.4	Q6ZN16-1
MAP3K15	ENST00000927253.1		c.2967-37G>A	intron	N/A	ENSP00000597312.1
MAP3K15	ENST00000947404.1		c.2931-37G>A	intron	N/A	ENSP00000617463.1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

11894

AN:

110595

Hom.:

1171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0451

Gnomad ASJ

AF:

0.0734

Gnomad EAS

AF:

0.00490

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.131

Gnomad NFE

AF:

0.0225

Gnomad OTH

AF:

0.0947

GnomAD2 exomes

AF:

0.0588

AC:

9570

AN:

162893

AF XY:

0.0567

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.0262

Gnomad ASJ exome

AF:

0.0732

Gnomad EAS exome

AF:

0.00291

Gnomad FIN exome

AF:

0.0232

Gnomad NFE exome

AF:

0.0252

Gnomad OTH exome

AF:

0.0475

GnomAD4 exome

AF:

0.0394

AC:

41991

AN:

1066215

Hom.:

1597

Cov.:

AF XY:

0.0424

AC XY:

14317

AN XY:

337937

show subpopulations

African (AFR)

AF:

0.326

AC:

8459

AN:

25943

American (AMR)

AF:

0.0307

AC:

1039

AN:

33871

Ashkenazi Jewish (ASJ)

AF:

0.0715

AC:

1275

AN:

17844

East Asian (EAS)

AF:

0.00478

AC:

143

AN:

29899

South Asian (SAS)

AF:

0.141

AC:

7060

AN:

50230

European-Finnish (FIN)

AF:

0.0245

AC:

970

AN:

39639

Middle Eastern (MID)

AF:

0.103

AC:

412

AN:

4009

European-Non Finnish (NFE)

AF:

0.0246

AC:

20192

AN:

819905

Other (OTH)

AF:

0.0544

AC:

2441

AN:

44875

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1297

2594

3892

5189

6486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

998

1996

2994

3992

4990

<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:

0.108

AC:

11906

AN:

110644

Hom.:

1172

Cov.:

AF XY:

0.0974

AC XY:

3211

AN XY:

32952

show subpopulations

African (AFR)

AF:

0.310

AC:

9361

AN:

30165

American (AMR)

AF:

0.0451

AC:

472

AN:

10475

Ashkenazi Jewish (ASJ)

AF:

0.0734

AC:

194

AN:

2642

East Asian (EAS)

AF:

0.00491

AC:

AN:

3459

South Asian (SAS)

AF:

0.121

AC:

316

AN:

2604

European-Finnish (FIN)

AF:

0.0189

AC:

114

AN:

6041

Middle Eastern (MID)

AF:

0.130

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0225

AC:

1190

AN:

52877

Other (OTH)

AF:

0.0935

AC:

140

AN:

1497

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

310

621

931

1242

1552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0741

Hom.:

693

Bravo

AF:

0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.30

(source)

DANN

Benign

0.76

PhyloP100

-1.4

Mutation Taster

=100/0

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

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over