chr2-173169843-C-A

Variant names:

• chr2-173169843-C-A
• NM_016653.3:c.198C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_016653.3(MAP3K20):​c.198C>A​(p.Ile66Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MAP3K20 NM_016653.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.33
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 2-173169843-C-A is Benign according to our data. Variant chr2-173169843-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3629020.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.33 with no splicing effect.

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.198C>A	p.Ile66Ile	synonymous	Exon 3 of 20	NP_057737.2	Q9NYL2-1
	MAP3K20	NM_133646.3		c.198C>A	p.Ile66Ile	synonymous	Exon 3 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.198C>A	p.Ile66Ile	synonymous	Exon 3 of 20	ENSP00000364361.3	Q9NYL2-1
	MAP3K20	ENST00000409176.6	TSL:1	c.198C>A	p.Ile66Ile	synonymous	Exon 3 of 20	ENSP00000387259.2	Q9NYL2-1
	MAP3K20	ENST00000338983.7	TSL:1	c.198C>A	p.Ile66Ile	synonymous	Exon 3 of 12	ENSP00000340257.3	Q9NYL2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461616 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727084

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111920

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		2.3
Mutation Taster		=282/18	polymorphism

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

Other links and lift over

hg19: chr2-174034571;