rs149230384

Variant names:

• chr2-173091043-C-A
• rs149230384
• NM_016653.3:c.12C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-173091043-C-A
• chr2-173091043-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_016653.3(MAP3K20):​c.12C>A​(p.Leu4Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L4L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MAP3K20 NM_016653.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.739
• 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 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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP7: Synonymous conserved (PhyloP=0.739 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.12C>A	p.Leu4Leu	synonymous	Exon 2 of 20	NP_057737.2	Q9NYL2-1
	MAP3K20	NM_133646.3		c.12C>A	p.Leu4Leu	synonymous	Exon 2 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.12C>A	p.Leu4Leu	synonymous	Exon 2 of 20	ENSP00000364361.3	Q9NYL2-1
	MAP3K20	ENST00000409176.6	TSL:1	c.12C>A	p.Leu4Leu	synonymous	Exon 2 of 20	ENSP00000387259.2	Q9NYL2-1
	MAP3K20	ENST00000338983.7	TSL:1	c.12C>A	p.Leu4Leu	synonymous	Exon 2 of 12	ENSP00000340257.3	Q9NYL2-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.74
PromoterAI		-0.073	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs149230384; hg19: chr2-173955771;