rs2582905

Positions:

• chr11-28488553-G-A

Variant summary

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

The ENST00000532947.2(METTL15):​c.*425-37925G>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,994 control chromosomes in the GnomAD database, including 27,509 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 0.59 (27509 hom., cov: 32)
• Consequence: METTL15 ENST00000532947.2 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL15	XR_007062458.1	n.1414-37925G>A		intron_variant, non_coding_transcript_variant
METTL15	XR_930849.3	n.1332-37925G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL15	ENST00000532947.2	c.*425-37925G>A		intron_variant, NMD_transcript_variant		5		ENSP00000489497

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88905 AN: 151876 Hom.: 27482 Cov.: 32

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.585 AC: 88977 AN: 151994 Hom.: 27509 Cov.: 32 AF XY: 0.589 AC XY: 43719 AN XY: 74266

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.546

Alfa AF: 0.500 Hom.: 18286

Bravo AF: 0.589

Asia WGS AF: 0.629 AC: 2188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.2
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2582905; hg19: chr11-28510100;