rs2347279

Positions:

• chr18-2538546-C-A
• chr18-2538546-C-T

Variant summary

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

The NM_022840.5(METTL4):​c.*454G>T variant causes a 3 prime UTR 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 NM_022840.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METTL4	NM_022840.5	c.*454G>T		3_prime_UTR_variant	9/9	ENST00000574538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL4	ENST00000574538.2	c.*454G>T		3_prime_UTR_variant	9/9	1	NM_022840.5	P1
METTL4	ENST00000573134.1	n.4174G>T		non_coding_transcript_exon_variant	7/7	1
METTL4	ENST00000319888.10	c.*521G>T		3_prime_UTR_variant	8/8	5
METTL4	ENST00000576251.5	c.*591G>T		3_prime_UTR_variant	4/4	2

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

Gnomad4 AFR exome AF: 0.423

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.0444

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.138

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

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0558

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.233

Alfa AF: 0.229 Hom.: 5345

Bravo AF: 0.253

Asia WGS AF: 0.123 AC: 428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs2347279; hg19: chr18-2538545;