Genetic Variant MAP3K9:c.820+17582G>A (chr14-70783085-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_001284230.2(MAP3K9):c.820+17582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 171,968 control chromosomes in the GnomAD database, including 999 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 0.10 ( 931 hom., cov: 32)

Exomes 𝑓: 0.088 ( 68 hom. )

Consequence

MAP3K9
NM_001284230.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0470

Publications

6 publications found

Variant links:

Genes affected

MAP3K9 (HGNC:6861): (mitogen-activated protein kinase kinase kinase 9) Enables protein serine/threonine kinase activity. Involved in protein autophosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

MAP3K9 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001284230.2, 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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284230.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAP3K9	NM_001284230.2	MANE Select	c.820+17582G>A	intron	N/A	NP_001271159.1	P80192-1
MAP3K9	NM_033141.4		c.820+17582G>A	intron	N/A	NP_149132.2
MAP3K9	NM_001284231.1		c.-16+138G>A	intron	N/A	NP_001271160.1	Q8NEB1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAP3K9	ENST00000554752.7	TSL:1 MANE Select	c.820+17582G>A	intron	N/A	ENSP00000451612.2	P80192-1
MAP3K9	ENST00000555993.6	TSL:1	c.820+17582G>A	intron	N/A	ENSP00000451263.2	P80192-4
MAP3K9	ENST00000553414.5	TSL:1	c.-99+138G>A	intron	N/A	ENSP00000451038.1	G3V347

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15459

AN:

152022

Hom.:

931

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0630

Gnomad ASJ

AF:

0.0588

Gnomad EAS

AF:

0.0331

Gnomad SAS

AF:

0.0423

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0844

Gnomad OTH

AF:

0.0932

GnomAD4 exome

AF:

0.0878

AC:

1740

AN:

19828

Hom.:

AF XY:

0.0860

AC XY:

834

AN XY:

9694

show subpopulations

African (AFR)

AF:

0.192

AC:

AN:

370

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0526

AC:

AN:

114

East Asian (EAS)

AF:

0.0139

AC:

AN:

South Asian (SAS)

AF:

0.0348

AC:

AN:

402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.0208

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0880

AC:

1600

AN:

18190

Other (OTH)

AF:

0.0770

AC:

AN:

610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

166

250

333

416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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:

0.102

AC:

15469

AN:

152140

Hom.:

931

Cov.:

AF XY:

0.100

AC XY:

7470

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.163

AC:

6780

AN:

41474

American (AMR)

AF:

0.0629

AC:

961

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0588

AC:

204

AN:

3470

East Asian (EAS)

AF:

0.0334

AC:

173

AN:

5182

South Asian (SAS)

AF:

0.0419

AC:

202

AN:

4816

European-Finnish (FIN)

AF:

0.107

AC:

1137

AN:

10594

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0845

AC:

5743

AN:

68002

Other (OTH)

AF:

0.0927

AC:

196

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

695

1390

2085

2780

3475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.0891

Hom.:

1650

Bravo

AF:

0.103

Asia WGS

AF:

0.0390

AC:

137

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

2.8

(source)

DANN

Benign

0.16

PhyloP100

0.047

PromoterAI

-0.017

Neutral

(source)

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