rs12145743

chr1-156730859-T-G

Variant summary

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

The NM_015997.4(METTL25B):c.112-1132T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,212 control chromosomes in the GnomAD database, including 5,662 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 0.24 (5662 hom., cov: 33)
• Consequence: METTL25B NM_015997.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

Genes affected

METTL25B (HGNC:24273): (methyltransferase like 25B) Predicted to enable rRNA (adenine-N6,N6-)-dimethyltransferase activity. Predicted to be involved in rRNA methylation. 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METTL25B	NM_015997.4	c.112-1132T>G		intron_variant		ENST00000368216.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL25B	ENST00000368216.9	c.112-1132T>G		intron_variant		1	NM_015997.4	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36546 AN: 152094 Hom.: 5659 Cov.: 33

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.240 AC: 36556 AN: 152212 Hom.: 5662 Cov.: 33 AF XY: 0.237 AC XY: 17627 AN XY: 74410

Gnomad4 AFR AF: 0.0640

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.279

Alfa AF: 0.326 Hom.: 17952

Bravo AF: 0.220

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.3
Dann	Benign	0.51

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: rs12145743; hg19: chr1-156700651;