18-2552887-G-A

Variant names:

• chr18-2552887-G-A
• rs10502302
• ENST00000573134.1:n.3008C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000573134.1(METTL4):​n.3008C>T variant causes a non coding transcript exon 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 ENST00000573134.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000573134.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL4	NM_022840.5	MANE Select	c.830-123C>T		intron	N/A	NP_073751.3
	METTL4	NM_001308401.2		c.830-123C>T		intron	N/A	NP_001295330.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL4	ENST00000573134.1	TSL:1	n.3008C>T		non_coding_transcript_exon	Exon 3 of 7
	METTL4	ENST00000574538.2	TSL:1 MANE Select	c.830-123C>T		intron	N/A	ENSP00000458290.1
	METTL4	ENST00000319888.10	TSL:5	c.830-123C>T		intron	N/A	ENSP00000320349.6

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

African (AFR) AF: 0.119 AC: 1522 AN: 12808

American (AMR) AF: 0.540 AC: 10796 AN: 19994

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 4238 AN: 14696

East Asian (EAS) AF: 0.620 AC: 19216 AN: 31008

South Asian (SAS) AF: 0.411 AC: 19344 AN: 47028

European-Finnish (FIN) AF: 0.414 AC: 13925 AN: 33602

Middle Eastern (MID) AF: 0.340 AC: 1229 AN: 3620

European-Non Finnish (NFE) AF: 0.371 AC: 106382 AN: 286484

Other (OTH) AF: 0.380 AC: 10261 AN: 27014

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

African (AFR) AF: 0.125 AC: 5191 AN: 41460

American (AMR) AF: 0.475 AC: 7267 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1059 AN: 3470

East Asian (EAS) AF: 0.632 AC: 3277 AN: 5182

South Asian (SAS) AF: 0.415 AC: 2001 AN: 4820

European-Finnish (FIN) AF: 0.435 AC: 4579 AN: 10520

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.378 AC: 25678 AN: 67932

Other (OTH) AF: 0.335 AC: 707 AN: 2108

Alfa AF: 0.357 Hom.: 1913

Bravo AF: 0.329

Asia WGS AF: 0.473 AC: 1646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.53
PhyloP100		0.56
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: rs10502302; hg19: chr18-2552886; COSMIC: COSV60603070; COSMIC: COSV60603070;