12-82380120-T-C

Position:

• chr12-82380120-T-C

Variant summary

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

The NM_032230.3(METTL25):​c.260-6683T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 152,208 control chromosomes in the GnomAD database, including 65,340 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 0.92 (65340 hom., cov: 32)
• Consequence: METTL25 NM_032230.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973

Genes affected

METTL25 (HGNC:26228): (methyltransferase like 25) Predicted to enable methyltransferase activity. Predicted to be involved in methylation. [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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL25	NM_032230.3	c.260-6683T>C		intron_variant		ENST00000248306.8	NP_115606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL25	ENST00000248306.8	c.260-6683T>C		intron_variant		1	NM_032230.3	ENSP00000248306	P1

Frequencies

GnomAD3 genomes AF: 0.925 AC: 140615 AN: 152090 Hom.: 65315 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.924 AC: 140694 AN: 152208 Hom.: 65340 Cov.: 32 AF XY: 0.926 AC XY: 68943 AN XY: 74422

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.944

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.991

Gnomad4 FIN AF: 0.973

Gnomad4 NFE AF: 0.963

Gnomad4 OTH AF: 0.924

Alfa AF: 0.947 Hom.: 3765

Bravo AF: 0.917

Asia WGS AF: 0.974 AC: 3386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.39
DANN	Benign	0.56

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: rs2401027; hg19: chr12-82773899;