rs3754741

chr2-173188491-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016653.3(MAP3K20):c.415+868A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,068 control chromosomes in the GnomAD database, including 9,019 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (9019 hom., cov: 31)
• Consequence: MAP3K20 NM_016653.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K20	NM_016653.3	c.415+868A>G		intron_variant		ENST00000375213.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K20	ENST00000375213.8	c.415+868A>G		intron_variant		1	NM_016653.3	P1
MAP3K20-AS1	ENST00000422703.5	n.338+4450T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46852 AN: 151954 Hom.: 9023 Cov.: 31

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.288

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.308 AC: 46844 AN: 152068 Hom.: 9019 Cov.: 31 AF XY: 0.307 AC XY: 22792 AN XY: 74306

Gnomad4 AFR AF: 0.0907

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.286

Alfa AF: 0.366 Hom.: 1930

Bravo AF: 0.277

Asia WGS AF: 0.246 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.9
Dann	Benign	0.60

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

Other links and lift over

dbSNP: rs3754741; hg19: chr2-174053219;