rs10502302

Positions:

• chr18-2552887-G-A

Variant summary

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

The ENST00000574538.2(METTL4):​c.830-123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 628,238 control chromosomes in the GnomAD database, including 48,611 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 0.33 (9795 hom., cov: 32)
  • Exomes 𝑓: 0.39 (38816 hom.)
• Consequence: METTL4 ENST00000574538.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565

Genes affected

METTL4 (HGNC:24726): (methyltransferase 4, N6-adenosine) Enables RNA methyltransferase activity and site-specific DNA-methyltransferase (adenine-specific) activity. Involved in nucleic acid metabolic process; regulation of RNA metabolic process; and regulation of mitochondrial DNA replication. Located in cytosol; mitochondrial matrix; and nucleus. [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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL4	NM_022840.5	c.830-123C>T		intron_variant		ENST00000574538.2	NP_073751.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL4	ENST00000574538.2	c.830-123C>T		intron_variant		1	NM_022840.5	ENSP00000458290	P1
METTL4	ENST00000573134.1	n.3008C>T		non_coding_transcript_exon_variant	3/7	1
METTL4	ENST00000319888.10	c.830-123C>T		intron_variant		5		ENSP00000320349
METTL4	ENST00000576251.5	c.25-123C>T		intron_variant		2		ENSP00000460774

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50109 AN: 151866 Hom.: 9786 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.324

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.392 AC: 186913 AN: 476254 Hom.: 38816 Cov.: 5 AF XY: 0.393 AC XY: 100294 AN XY: 255196

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.540

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.620

Gnomad4 SAS exome AF: 0.411

Gnomad4 FIN exome AF: 0.414

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.380

GnomAD4 genome AF: 0.330 AC: 50133 AN: 151984 Hom.: 9795 Cov.: 32 AF XY: 0.339 AC XY: 25138 AN XY: 74260

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.335

Alfa AF: 0.365 Hom.: 1904

Bravo AF: 0.329

Asia WGS AF: 0.473 AC: 1646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.53

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: rs10502302; hg19: chr18-2552886; COSMIC: COSV60603070; COSMIC: COSV60603070;