2-173224878-T-G

Variant names:

• chr2-173224878-T-G
• rs10497401
• ENST00000338983.7:c.*3348T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133646.3(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 NM_133646.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480
• 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133646.3. 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.988-4811T>G		intron	N/A	NP_057737.2	Q9NYL2-1
	MAP3K20	NM_133646.3		c.*3348T>G		3_prime_UTR	Exon 12 of 12	NP_598407.1	Q9NYL2-2
	MAP3K20-AS1	NR_033882.1		n.464-9042A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K20	ENST00000338983.7	TSL:1	c.*3348T>G		3_prime_UTR	Exon 12 of 12	ENSP00000340257.3	Q9NYL2-2
	MAP3K20	ENST00000375213.8	TSL:1 MANE Select	c.988-4811T>G		intron	N/A	ENSP00000364361.3	Q9NYL2-1
	MAP3K20	ENST00000409176.6	TSL:1	c.988-4811T>G		intron	N/A	ENSP00000387259.2	Q9NYL2-1

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

African (AFR) AF: 0.229 AC: 3605 AN: 15752

American (AMR) AF: 0.221 AC: 217 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 690 AN: 5148

East Asian (EAS) AF: 0.0678 AC: 246 AN: 3626

South Asian (SAS) AF: 0.0754 AC: 1240 AN: 16454

European-Finnish (FIN) AF: 0.127 AC: 35 AN: 276

Middle Eastern (MID) AF: 0.166 AC: 269 AN: 1616

European-Non Finnish (NFE) AF: 0.136 AC: 103605 AN: 761250

Other (OTH) AF: 0.132 AC: 3591 AN: 27284

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

African (AFR) AF: 0.222 AC: 9206 AN: 41536

American (AMR) AF: 0.204 AC: 3113 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3472

East Asian (EAS) AF: 0.0619 AC: 321 AN: 5188

South Asian (SAS) AF: 0.0728 AC: 351 AN: 4824

European-Finnish (FIN) AF: 0.142 AC: 1504 AN: 10612

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.143 AC: 9758 AN: 68006

Other (OTH) AF: 0.177 AC: 375 AN: 2114

Alfa AF: 0.160 Hom.: 2677

Bravo AF: 0.175

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		-0.048
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs10497401; hg19: chr2-174089606;