rs11601602

Positions:

• chr11-28212221-A-G

Variant summary

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

The NM_001113528.2(METTL15):​c.407+1023A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,908 control chromosomes in the GnomAD database, including 3,192 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 0.19 (3192 hom., cov: 31)
• Consequence: METTL15 NM_001113528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL15	NM_001113528.2	c.407+1023A>G		intron_variant		ENST00000407364.8	NP_001107000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL15	ENST00000407364.8	c.407+1023A>G		intron_variant		5	NM_001113528.2	ENSP00000384369.3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29042 AN: 151790 Hom.: 3195 Cov.: 31

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0782

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.191 AC: 29026 AN: 151908 Hom.: 3192 Cov.: 31 AF XY: 0.193 AC XY: 14337 AN XY: 74240

Gnomad4 AFR AF: 0.0985

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0780

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.217

Alfa AF: 0.215 Hom.: 1455

Bravo AF: 0.179

Asia WGS AF: 0.101 AC: 351 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11601602; hg19: chr11-28233768;