2-173224878-T-G

Position:

• chr2-173224878-T-G

Variant summary

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

The ENST00000338983.7(MAP3K20):​c.*3348T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 984,638 control chromosomes in the GnomAD database, including 10,259 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 0.17 (2256 hom., cov: 33)
  • Exomes 𝑓: 0.14 (8003 hom.)
• Consequence: MAP3K20 ENST00000338983.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K20	NM_016653.3	c.988-4811T>G		intron_variant		ENST00000375213.8	NP_057737.2
MAP3K20-AS1	NR_033882.1	n.464-9042A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K20	ENST00000375213.8	c.988-4811T>G		intron_variant		1	NM_016653.3	ENSP00000364361	P1
MAP3K20-AS1	ENST00000422703.5	n.111-17220A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25296 AN: 152130 Hom.: 2255 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0621

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.136 AC: 113498 AN: 832390 Hom.: 8003 Cov.: 31 AF XY: 0.135 AC XY: 52072 AN XY: 384428

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.0678

Gnomad4 SAS exome AF: 0.0754

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.166 AC: 25311 AN: 152248 Hom.: 2256 Cov.: 33 AF XY: 0.164 AC XY: 12229 AN XY: 74440

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.0619

Gnomad4 SAS AF: 0.0728

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.177

Alfa AF: 0.157 Hom.: 1984

Bravo AF: 0.175

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.49

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: rs10497401; hg19: chr2-174089606;