rs9514044

Positions:

• chr13-102693115-T-C

Variant summary

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

The NM_001010977.3(METTL21C):​c.130+1254A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,012 control chromosomes in the GnomAD database, including 10,030 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 0.33 (10030 hom., cov: 32)
• Consequence: METTL21C NM_001010977.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.03

Genes affected

METTL21C (HGNC:33717): (methyltransferase 21C, AARS1 lysine) Enables heat shock protein binding activity and protein-lysine N-methyltransferase activity. Involved in protein methylation. Located in nucleus. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METTL21C	NM_001010977.3	c.130+1254A>G		intron_variant		ENST00000267273.7
METTL21C	XM_047430117.1	c.130+1254A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL21C	ENST00000267273.7	c.130+1254A>G		intron_variant		1	NM_001010977.3	P1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49874 AN: 151894 Hom.: 10016 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.329 AC: 49937 AN: 152012 Hom.: 10030 Cov.: 32 AF XY: 0.322 AC XY: 23954 AN XY: 74286

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.325

Alfa AF: 0.262 Hom.: 8406

Bravo AF: 0.343

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.020
DANN	Benign	0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs9514044; hg19: chr13-103345465;