18-2538546-C-A

Variant names:

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

Variant summary

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

The ENST00000573134.1(METTL4):​n.4174G>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 0.254 in 154,356 control chromosomes in the GnomAD database, including 5,393 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 0.26 (5347 hom., cov: 32)
  • Exomes 𝑓: 0.18 (46 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 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.*454G>T		3_prime_UTR	Exon 9 of 9	NP_073751.3
	METTL4	NM_001308401.2		c.*521G>T		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>T		non_coding_transcript_exon	Exon 7 of 7
	METTL4	ENST00000574538.2	TSL:1 MANE Select	c.*454G>T		3_prime_UTR	Exon 9 of 9	ENSP00000458290.1
	METTL4	ENST00000319888.10	TSL:5	c.*521G>T		3_prime_UTR	Exon 8 of 8	ENSP00000320349.6

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38848 AN: 151994 Hom.: 5346 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0556

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.176 AC: 394 AN: 2244 Hom.: 46 Cov.: 0 AF XY: 0.164 AC XY: 201 AN XY: 1224

African (AFR) AF: 0.423 AC: 11 AN: 26

American (AMR) AF: 0.117 AC: 34 AN: 290

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 6 AN: 24

East Asian (EAS) AF: 0.0444 AC: 4 AN: 90

South Asian (SAS) AF: 0.135 AC: 26 AN: 192

European-Finnish (FIN) AF: 0.133 AC: 4 AN: 30

Middle Eastern (MID) AF: 0.125 AC: 1 AN: 8

European-Non Finnish (NFE) AF: 0.197 AC: 297 AN: 1504

Other (OTH) AF: 0.138 AC: 11 AN: 80

GnomAD4 genome AF: 0.256 AC: 38880 AN: 152112 Hom.: 5347 Cov.: 32 AF XY: 0.252 AC XY: 18732 AN XY: 74370

African (AFR) AF: 0.349 AC: 14479 AN: 41478

American (AMR) AF: 0.194 AC: 2955 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 585 AN: 3472

East Asian (EAS) AF: 0.0558 AC: 289 AN: 5182

South Asian (SAS) AF: 0.153 AC: 738 AN: 4824

European-Finnish (FIN) AF: 0.245 AC: 2593 AN: 10592

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16607 AN: 67978

Other (OTH) AF: 0.233 AC: 494 AN: 2116

Alfa AF: 0.232 Hom.: 7038

Bravo AF: 0.253

Asia WGS AF: 0.123 AC: 428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.70
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;