chr18-2538546-C-T

Variant names:

• chr18-2538546-C-T
• rs2347279
• ENST00000573134.1:n.4174G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000573134.1(METTL4):​n.4174G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: METTL4 ENST00000573134.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.*454G>A		3_prime_UTR	Exon 9 of 9	NP_073751.3
	METTL4	NM_001308401.2		c.*521G>A		3_prime_UTR	Exon 8 of 8	NP_001295330.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL4	ENST00000573134.1	TSL:1	n.4174G>A		non_coding_transcript_exon	Exon 7 of 7
	METTL4	ENST00000574538.2	TSL:1 MANE Select	c.*454G>A		3_prime_UTR	Exon 9 of 9	ENSP00000458290.1
	METTL4	ENST00000319888.10	TSL:5	c.*521G>A		3_prime_UTR	Exon 8 of 8	ENSP00000320349.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2260 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1232

African (AFR) AF: 0.00 AC: 0 AN: 26

American (AMR) AF: 0.00 AC: 0 AN: 292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24

East Asian (EAS) AF: 0.00 AC: 0 AN: 92

South Asian (SAS) AF: 0.00 AC: 0 AN: 194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1514

Other (OTH) AF: 0.00 AC: 0 AN: 80

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 7038

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.61
PhyloP100		-0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2347279; hg19: chr18-2538545;