chr2-173190918-T-C

Variant names:

• chr2-173190918-T-C
• rs35853276
• NM_016653.3:c.439T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016653.3(MAP3K20):​c.439T>C​(p.Leu147Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 1,596,050 control chromosomes in the GnomAD database, including 9,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1928 hom., cov: 32)
  • Exomes 𝑓: 0.096 (8004 hom.)
• Consequence: MAP3K20 NM_016653.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.949
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 2-173190918-T-C is Benign according to our data. Variant chr2-173190918-T-C is described in ClinVar as Benign. ClinVar VariationId is 1174343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.949 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

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.439T>C	p.Leu147Leu	synonymous	Exon 6 of 20	NP_057737.2	Q9NYL2-1
	MAP3K20	NM_133646.3		c.439T>C	p.Leu147Leu	synonymous	Exon 6 of 12	NP_598407.1	Q9NYL2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K20	ENST00000375213.8	TSL:1 MANE Select	c.439T>C	p.Leu147Leu	synonymous	Exon 6 of 20	ENSP00000364361.3	Q9NYL2-1
	MAP3K20	ENST00000409176.6	TSL:1	c.439T>C	p.Leu147Leu	synonymous	Exon 6 of 20	ENSP00000387259.2	Q9NYL2-1
	MAP3K20	ENST00000338983.7	TSL:1	c.439T>C	p.Leu147Leu	synonymous	Exon 6 of 12	ENSP00000340257.3	Q9NYL2-2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20859 AN: 152082 Hom.: 1926 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.138

GnomAD2 exomes AF: 0.101 AC: 24821 AN: 246928 AF XY: 0.102

Gnomad AFR exome AF: 0.261

Gnomad AMR exome AF: 0.0627

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.000440

Gnomad FIN exome AF: 0.0501

Gnomad NFE exome AF: 0.0982

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.0959 AC: 138396 AN: 1443850 Hom.: 8004 Cov.: 30 AF XY: 0.0981 AC XY: 70528 AN XY: 718852

African (AFR) AF: 0.263 AC: 8537 AN: 32420

American (AMR) AF: 0.0683 AC: 2997 AN: 43854

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 4441 AN: 25782

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39612

South Asian (SAS) AF: 0.142 AC: 12014 AN: 84534

European-Finnish (FIN) AF: 0.0495 AC: 2640 AN: 53324

Middle Eastern (MID) AF: 0.225 AC: 1267 AN: 5640

European-Non Finnish (NFE) AF: 0.0908 AC: 99747 AN: 1099046

Other (OTH) AF: 0.113 AC: 6740 AN: 59638

GnomAD4 genome AF: 0.137 AC: 20884 AN: 152200 Hom.: 1928 Cov.: 32 AF XY: 0.135 AC XY: 10064 AN XY: 74418

African (AFR) AF: 0.257 AC: 10651 AN: 41492

American (AMR) AF: 0.100 AC: 1533 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3468

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.135 AC: 652 AN: 4822

European-Finnish (FIN) AF: 0.0494 AC: 524 AN: 10612

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.0959 AC: 6518 AN: 68002

Other (OTH) AF: 0.138 AC: 291 AN: 2116

Alfa AF: 0.120 Hom.: 685

Bravo AF: 0.146

Asia WGS AF: 0.0730 AC: 255 AN: 3478

EpiCase AF: 0.118

EpiControl AF: 0.113

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	MAP3K20-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.2
DANN	Benign	0.87
PhyloP100		0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35853276; hg19: chr2-174055646; COSMIC: COSV59104478; COSMIC: COSV59104478;