2-173091097-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS1

The NM_016653.3(MAP3K20):c.66C>T(p.Cys22Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000492 in 1,613,058 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00037 ( 1 hom. )

Consequence

MAP3K20
NM_016653.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.28

Publications

3 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 Gene-Disease associations (from GenCC):

myopathy, centronuclear, 6, with fiber-type disproportion
Inheritance: AR Classification: STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics
split hand-foot malformation
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
congenital fiber-type disproportion myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
split-foot malformation-mesoaxial polydactyly syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

MAP3K20 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 2-173091097-C-T is Benign according to our data. Variant chr2-173091097-C-T is described in ClinVar as Benign. ClinVar VariationId is 1531699.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00162 (246/151676) while in subpopulation AFR AF = 0.00484 (200/41340). AF 95% confidence interval is 0.00429. There are 0 homozygotes in GnomAd4. There are 109 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016653.3. 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
	MAP3K20	NM_016653.3	MANE Select	c.66C>T	p.Cys22Cys	synonymous	Exon 2 of 20	NP_057737.2	Q9NYL2-1
	MAP3K20	NM_133646.3		c.66C>T	p.Cys22Cys	synonymous	Exon 2 of 12	NP_598407.1	Q9NYL2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAP3K20	ENST00000375213.8	TSL:1 MANE Select	c.66C>T	p.Cys22Cys	synonymous	Exon 2 of 20	ENSP00000364361.3	Q9NYL2-1
MAP3K20	ENST00000409176.6	TSL:1	c.66C>T	p.Cys22Cys	synonymous	Exon 2 of 20	ENSP00000387259.2	Q9NYL2-1
MAP3K20	ENST00000338983.7	TSL:1	c.66C>T	p.Cys22Cys	synonymous	Exon 2 of 12	ENSP00000340257.3	Q9NYL2-2

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

244

AN:

151558

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00480

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000855

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.0000953

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00145

GnomAD2 exomes

AF:

0.000530

AC:

133

AN:

251134

AF XY:

0.000427

show subpopulations

Gnomad AFR exome

AF:

0.00499

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000375

AC:

548

AN:

1461382

Hom.:

Cov.:

AF XY:

0.000345

AC XY:

251

AN XY:

727000

show subpopulations

African (AFR)

AF:

0.00499

AC:

167

AN:

33466

American (AMR)

AF:

0.000403

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000280

AC:

311

AN:

1111688

Other (OTH)

AF:

0.000729

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00162

AC:

246

AN:

151676

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

109

AN XY:

74108

show subpopulations

African (AFR)

AF:

0.00484

AC:

200

AN:

41340

American (AMR)

AF:

0.000854

AC:

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000210

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.0000953

AC:

AN:

10498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

67908

Other (OTH)

AF:

0.00143

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000916

Hom.:

Bravo

AF:

0.00192

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

1.3

PromoterAI

-0.034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=91/9

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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