rs7569963

Variant names:

• chr2-207608460-G-A
• rs7569963
• ENST00000458426.5:c.259+13346C>T

Variant summary

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

The NM_001393563.1(METTL21A):​c.313+12181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,636 control chromosomes in the GnomAD database, including 4,566 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 0.22 (4566 hom., cov: 31)
• Consequence: METTL21A NM_001393563.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 21 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393563.1. 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_001393563.1		c.313+12181C>T		intron	N/A	NP_001380492.1
	METTL21A	NM_001308021.3		c.259+13346C>T		intron	N/A	NP_001294950.1
	METTL21A	NM_001330132.3		c.259+13346C>T		intron	N/A	NP_001317061.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL21A	ENST00000458426.5	TSL:1	c.259+13346C>T		intron	N/A	ENSP00000389684.1
	METTL21A	ENST00000432416.5	TSL:3	c.259+13346C>T		intron	N/A	ENSP00000416570.1
	METTL21A	ENST00000425132.5	TSL:2	c.259+13346C>T		intron	N/A	ENSP00000400730.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 32965 AN: 151518 Hom.: 4565 Cov.: 31

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.217 AC: 32970 AN: 151636 Hom.: 4566 Cov.: 31 AF XY: 0.215 AC XY: 15940 AN XY: 74046

African (AFR) AF: 0.0556 AC: 2301 AN: 41352

American (AMR) AF: 0.267 AC: 4071 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3466

East Asian (EAS) AF: 0.124 AC: 642 AN: 5158

South Asian (SAS) AF: 0.305 AC: 1461 AN: 4796

European-Finnish (FIN) AF: 0.275 AC: 2862 AN: 10416

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20314 AN: 67890

Other (OTH) AF: 0.194 AC: 409 AN: 2106

Alfa AF: 0.241 Hom.: 2448

Bravo AF: 0.213

Asia WGS AF: 0.206 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.95
DANN	Benign	0.32
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7569963; hg19: chr2-208473184;