Genetic Variant MAP3K20:c.*3348T>G (chr2-173224878-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000338983.7(MAP3K20):c.*3348T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 984,638 control chromosomes in the GnomAD database, including 10,259 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 0.17 ( 2256 hom., cov: 33)

Exomes 𝑓: 0.14 ( 8003 hom. )

Consequence

MAP3K20
ENST00000338983.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0480

Publications

7 publications found

Variant links:

Genes affected

MAP3K20 (HGNC:17797): (mitogen-activated protein kinase kinase kinase 20) This gene is a member of the MAPKKK family of signal transduction molecules and encodes a protein with an N-terminal kinase catalytic domain, followed by a leucine zipper motif and a sterile-alpha motif (SAM). This magnesium-binding protein forms homodimers and is located in the cytoplasm. The protein mediates gamma radiation signaling leading to cell cycle arrest and activity of this protein plays a role in cell cycle checkpoint regulation in cells. The protein also has pro-apoptotic activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

MAP3K20 links:

MAP3K20-AS1 (HGNC:27935): (MAP3K20 antisense RNA 1)

MAP3K20-AS1 links:

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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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K20	NM_016653.3 link	c.988-4811T>G		intron_variant	Intron 11 of 19	ENST00000375213.8	NP_057737.2	Q9NYL2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K20	ENST00000375213.8 link	c.988-4811T>G		intron_variant	Intron 11 of 19	1	NM_016653.3	ENSP00000364361.3		Q9NYL2-1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25296

AN:

152130

Hom.:

2255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.178

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.0621

Gnomad SAS

AF:

0.0731

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.180

GnomAD4 exome

AF:

0.136

AC:

113498

AN:

832390

Hom.:

8003

Cov.:

AF XY:

0.135

AC XY:

52072

AN XY:

384428

show subpopulations

African (AFR)

AF:

0.229

AC:

3605

AN:

15752

American (AMR)

AF:

0.221

AC:

217

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

690

AN:

5148

East Asian (EAS)

AF:

0.0678

AC:

246

AN:

3626

South Asian (SAS)

AF:

0.0754

AC:

1240

AN:

16454

European-Finnish (FIN)

AF:

0.127

AC:

AN:

276

Middle Eastern (MID)

AF:

0.166

AC:

269

AN:

1616

European-Non Finnish (NFE)

AF:

0.136

AC:

103605

AN:

761250

Other (OTH)

AF:

0.132

AC:

3591

AN:

27284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

5069

10139

15208

20278

25347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5148

10296

15444

20592

25740

<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:

0.166

AC:

25311

AN:

152248

Hom.:

2256

Cov.:

AF XY:

0.164

AC XY:

12229

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.222

AC:

9206

AN:

41536

American (AMR)

AF:

0.204

AC:

3113

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

468

AN:

3472

East Asian (EAS)

AF:

0.0619

AC:

321

AN:

5188

South Asian (SAS)

AF:

0.0728

AC:

351

AN:

4824

European-Finnish (FIN)

AF:

0.142

AC:

1504

AN:

10612

Middle Eastern (MID)

AF:

0.182

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.143

AC:

9758

AN:

68006

Other (OTH)

AF:

0.177

AC:

375

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1083

2167

3250

4334

5417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.160

Hom.:

2677

Bravo

AF:

0.175

Asia WGS

AF:

0.106

AC:

370

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.5

(source)

DANN

Benign

0.49

PhyloP100

-0.048

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

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