rs6502244

Variant names:

• chr17-2450015-T-C
• rs6502244
• NM_024086.4:c.729-8456A>G

Variant summary

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

The NM_024086.4(METTL16):​c.729-8456A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,064 control chromosomes in the GnomAD database, including 9,593 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 0.27 (9593 hom., cov: 32)
• Consequence: METTL16 NM_024086.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490
• Publications: 7 publications found

Genes affected

METTL16 (HGNC:28484): (methyltransferase 16, RNA N6-adenosine) Enables RNA binding activity and RNA methyltransferase activity. Involved in RNA modification and regulation of mRNA metabolic process. Located in cytoplasm 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL16	NM_024086.4	c.729-8456A>G		intron_variant	Intron 6 of 9	ENST00000263092.11	NP_076991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL16	ENST00000263092.11	c.729-8456A>G		intron_variant	Intron 6 of 9	1	NM_024086.4	ENSP00000263092.5
METTL16	ENST00000571669.6	n.734-8456A>G		intron_variant	Intron 5 of 8	5
METTL16	ENST00000574752.5	n.*106-8456A>G		intron_variant	Intron 5 of 9	5		ENSP00000460207.1
METTL16	ENST00000576556.5	n.*106-8456A>G		intron_variant	Intron 4 of 7	2		ENSP00000460775.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41556 AN: 151946 Hom.: 9567 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.243

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.274 AC: 41643 AN: 152064 Hom.: 9593 Cov.: 32 AF XY: 0.266 AC XY: 19818 AN XY: 74374

African (AFR) AF: 0.633 AC: 26232 AN: 41416

American (AMR) AF: 0.207 AC: 3156 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3470

East Asian (EAS) AF: 0.0181 AC: 94 AN: 5188

South Asian (SAS) AF: 0.257 AC: 1238 AN: 4822

European-Finnish (FIN) AF: 0.0668 AC: 708 AN: 10594

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8821 AN: 67982

Other (OTH) AF: 0.245 AC: 516 AN: 2110

Alfa AF: 0.219 Hom.: 1047

Bravo AF: 0.299

Asia WGS AF: 0.212 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		0.49
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: rs6502244; hg19: chr17-2353309;