rs12145743

Variant names:

• chr1-156730859-T-G
• rs12145743
• NM_015997.4:c.112-1132T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 68 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
METTL25B	NM_015997.4	c.112-1132T>G		intron_variant	Intron 1 of 7	ENST00000368216.9	NP_057081.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL25B	ENST00000368216.9	c.112-1132T>G		intron_variant	Intron 1 of 7	1	NM_015997.4	ENSP00000357199.4

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

African (AFR) AF: 0.0640 AC: 2659 AN: 41568

American (AMR) AF: 0.218 AC: 3339 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1043 AN: 3466

East Asian (EAS) AF: 0.112 AC: 580 AN: 5186

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4826

European-Finnish (FIN) AF: 0.324 AC: 3420 AN: 10570

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23543 AN: 67986

Other (OTH) AF: 0.279 AC: 591 AN: 2116

Alfa AF: 0.316 Hom.: 33044

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
PhyloP100		-0.055
Mutation Taster		=100/0	polymorphism (auto)

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: rs12145743; hg19: chr1-156700651;