chr2-207624377-C-A

Variant names:

• chr2-207624377-C-A
• rs4234080
• NM_001127395.5:c.-2G>T

Variant summary

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

The NM_001127395.5(METTL21A):​c.-2G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,611,738 control chromosomes in the GnomAD database, including 26,940 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 0.23 (4893 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22047 hom.)
• Consequence: METTL21A NM_001127395.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• Publications: 22 publications found

Genes affected

METTL21A (HGNC:30476): (methyltransferase 21A, HSPA lysine) Enables ATPase binding activity; Hsp70 protein binding activity; and protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127395.5. 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
	METTL21A	NM_001127395.5	MANE Select	c.-2G>T		5_prime_UTR	Exon 2 of 4	NP_001120867.1	Q8WXB1-1
	METTL21A	NM_001330137.2		c.-2G>T		5_prime_UTR	Exon 2 of 5	NP_001317066.1	H7BXH9
	METTL21A	NM_001330130.2		c.-2G>T		5_prime_UTR	Exon 2 of 4	NP_001317059.1	Q8WXB1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL21A	ENST00000411432.6	TSL:2 MANE Select	c.-2G>T		5_prime_UTR	Exon 2 of 4	ENSP00000415115.1	Q8WXB1-1
	METTL21A	ENST00000406927.6	TSL:1	c.-2G>T		5_prime_UTR	Exon 2 of 4	ENSP00000385481.2	Q8WXB1-1
	METTL21A	ENST00000448007.6	TSL:1	c.-2G>T		5_prime_UTR	Exon 2 of 4	ENSP00000407622.2	Q8WXB1-1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35183 AN: 151944 Hom.: 4884 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.235

GnomAD2 exomes AF: 0.193 AC: 48026 AN: 248888 AF XY: 0.186

Gnomad AFR exome AF: 0.393

Gnomad AMR exome AF: 0.284

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.168

Gnomad FIN exome AF: 0.138

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.168 AC: 245273 AN: 1459676 Hom.: 22047 Cov.: 31 AF XY: 0.167 AC XY: 120966 AN XY: 726150

African (AFR) AF: 0.394 AC: 13132 AN: 33366

American (AMR) AF: 0.279 AC: 12372 AN: 44350

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 5239 AN: 26058

East Asian (EAS) AF: 0.178 AC: 7060 AN: 39632

South Asian (SAS) AF: 0.163 AC: 14045 AN: 86020

European-Finnish (FIN) AF: 0.140 AC: 7454 AN: 53214

Middle Eastern (MID) AF: 0.238 AC: 1304 AN: 5480

European-Non Finnish (NFE) AF: 0.156 AC: 173570 AN: 1111264

Other (OTH) AF: 0.184 AC: 11097 AN: 60292

GnomAD4 genome AF: 0.232 AC: 35229 AN: 152062 Hom.: 4893 Cov.: 32 AF XY: 0.233 AC XY: 17299 AN XY: 74356

African (AFR) AF: 0.388 AC: 16069 AN: 41420

American (AMR) AF: 0.270 AC: 4124 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3472

East Asian (EAS) AF: 0.167 AC: 862 AN: 5160

South Asian (SAS) AF: 0.167 AC: 808 AN: 4826

European-Finnish (FIN) AF: 0.141 AC: 1495 AN: 10578

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10337 AN: 68010

Other (OTH) AF: 0.242 AC: 511 AN: 2108

Alfa AF: 0.198 Hom.: 6148

Bravo AF: 0.248

Asia WGS AF: 0.228 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.5
DANN	Benign	0.83
PhyloP100		0.090
PromoterAI		0.071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4234080; hg19: chr2-208489101; COSMIC: COSV55881172;