rs10501098

Variant names:

• chr11-28414952-G-A
• rs10501098
• ENST00000532947.2:n.*359-9347G>A

Variant summary

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

The ENST00000532947.2(METTL15):​n.*359-9347G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 152,272 control chromosomes in the GnomAD database, including 404 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 0.055 (404 hom., cov: 32)
• Consequence: METTL15 ENST00000532947.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 2 publications found

Genes affected

METTL15 (HGNC:26606): (methyltransferase 15, mitochondrial 12S rRNA N4-cytidine) Predicted to enable rRNA (cytosine-N4-)-methyltransferase activity. Predicted to be involved in rRNA base methylation. Predicted to be located in mitochondrial matrix. Predicted to be integral component of membrane. [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 = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL15	XR_007062458.1	n.1348-9347G>A		intron_variant	Intron 9 of 11
METTL15	XR_930849.3	n.1266-9347G>A		intron_variant	Intron 8 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL15	ENST00000532947.2	n.*359-9347G>A		intron_variant	Intron 5 of 7	5		ENSP00000489497.1

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8348 AN: 152154 Hom.: 399 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.0482

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0171

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0283

Gnomad OTH AF: 0.0397

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

GnomAD4 genome AF: 0.0549 AC: 8363 AN: 152272 Hom.: 404 Cov.: 32 AF XY: 0.0534 AC XY: 3973 AN XY: 74460

African (AFR) AF: 0.129 AC: 5369 AN: 41544

American (AMR) AF: 0.0298 AC: 456 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0482 AC: 167 AN: 3468

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4824

European-Finnish (FIN) AF: 0.0171 AC: 181 AN: 10606

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0283 AC: 1924 AN: 68032

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0340 Hom.: 193

Bravo AF: 0.0575

Asia WGS AF: 0.0180 AC: 63 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.090
DANN	Benign	0.48
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs10501098; hg19: chr11-28436499;