rs10501098

Positions:

• chr11-28414952-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

METTL15 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
METTL15	XR_007062458.1	n.1348-9347G>A		intron_variant
METTL15	XR_930849.3	n.1266-9347G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL15	ENST00000532947.2	n.*359-9347G>A		intron_variant		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

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0298

Gnomad4 ASJ AF: 0.0482

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.0171

Gnomad4 NFE AF: 0.0283

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0396 Hom.: 43

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10501098; hg19: chr11-28436499;