rs11826168

Variant names:

• chr11-28496555-T-C
• rs11826168
• ENST00000532947.2:n.*425-29923T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000532947.2(METTL15):​n.*425-29923T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0071 in 152,310 control chromosomes in the GnomAD database, including 8 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 0.0071 (8 hom., cov: 33)
• Consequence: METTL15 ENST00000532947.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 1 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=-0.91).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0071 (1081/152310) while in subpopulation AFR AF = 0.0236 (981/41552). AF 95% confidence interval is 0.0224. There are 8 homozygotes in GnomAd4. There are 516 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL15	XR_007062458.1	n.1414-29923T>C		intron_variant	Intron 10 of 11
METTL15	XR_930849.3	n.1332-29923T>C		intron_variant	Intron 9 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL15	ENST00000532947.2	n.*425-29923T>C		intron_variant	Intron 6 of 7	5		ENSP00000489497.1

Frequencies

GnomAD3 genomes AF: 0.00705 AC: 1073 AN: 152192 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00574

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

GnomAD4 genome AF: 0.00710 AC: 1081 AN: 152310 Hom.: 8 Cov.: 33 AF XY: 0.00693 AC XY: 516 AN XY: 74502

African (AFR) AF: 0.0236 AC: 981 AN: 41552

American (AMR) AF: 0.00418 AC: 64 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68030

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00605 Hom.: 0

Bravo AF: 0.00785

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	10
DANN	Benign	0.51
PhyloP100		-0.14

Splicing

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

Other links and lift over

dbSNP: rs11826168; hg19: chr11-28518102;