2-173091097-C-T

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.28
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP3K20NM_016653.3 linkc.66C>T p.Cys22Cys synonymous_variant Exon 2 of 20 ENST00000375213.8 NP_057737.2 Q9NYL2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAP3K20ENST00000375213.8 linkc.66C>T p.Cys22Cys synonymous_variant Exon 2 of 20 1 NM_016653.3 ENSP00000364361.3 Q9NYL2-1

Frequencies

GnomAD3 genomes
AF:
0.00161
AC:
244
AN:
151558
Hom.:
0
Cov.:
31
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
GnomAD3 exomes
AF:
0.000530
AC:
133
AN:
251134
Hom.:
1
AF XY:
0.000427
AC XY:
58
AN XY:
135720
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 SAS exome
AF:
0.0000980
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.:
1
Cov.:
31
AF XY:
0.000345
AC XY:
251
AN XY:
727000
show subpopulations
Gnomad4 AFR exome
AF:
0.00499
Gnomad4 AMR exome
AF:
0.000403
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000280
Gnomad4 OTH exome
AF:
0.000729
GnomAD4 genome
AF:
0.00162
AC:
246
AN:
151676
Hom.:
0
Cov.:
31
AF XY:
0.00147
AC XY:
109
AN XY:
74108
show subpopulations
Gnomad4 AFR
AF:
0.00484
Gnomad4 AMR
AF:
0.000854
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000210
Gnomad4 FIN
AF:
0.0000953
Gnomad4 NFE
AF:
0.000412
Gnomad4 OTH
AF:
0.00143
Alfa
AF:
0.000916
Hom.:
0
Bravo
AF:
0.00192
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000237

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jan 21, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.25
CADD
Benign
13
DANN
Benign
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147113074; hg19: chr2-173955825; COSMIC: COSV59102802; API