11-28113470-C-A

Variant names:

• chr11-28113470-C-A
• rs530544431
• NM_001113528.2:c.136C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001113528.2(METTL15):​c.136C>A​(p.Arg46Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,066 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: METTL15 NM_001113528.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-0.586 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113528.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL15	NM_001113528.2	MANE Select	c.136C>A	p.Arg46Arg	synonymous	Exon 3 of 7	NP_001107000.1	A6NJ78-1
	METTL15	NM_001297775.2		c.136C>A	p.Arg46Arg	synonymous	Exon 3 of 7	NP_001284704.1	A6NJ78-4
	METTL15	NM_152636.3		c.136C>A	p.Arg46Arg	synonymous	Exon 3 of 8	NP_689849.2	A6NJ78-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL15	ENST00000407364.8	TSL:5 MANE Select	c.136C>A	p.Arg46Arg	synonymous	Exon 3 of 7	ENSP00000384369.3	A6NJ78-1
	METTL15	ENST00000406787.7	TSL:1	c.136C>A	p.Arg46Arg	synonymous	Exon 3 of 7	ENSP00000385507.3	A6NJ78-4
	METTL15	ENST00000437814.1	TSL:1	n.136C>A		non_coding_transcript_exon	Exon 2 of 5	ENSP00000392806.1	A6NJ78-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460066 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726312

African (AFR) AF: 0.0000299 AC: 1 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4602

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111756

Other (OTH) AF: 0.00 AC: 0 AN: 60228

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		-0.59

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

Other links and lift over

dbSNP: rs530544431; hg19: chr11-28135017;