17-2463291-T-C

Variant names:

• chr17-2463291-T-C
• rs4268798
• NM_024086.4:c.728+917A>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.728+917A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,962 control chromosomes in the GnomAD database, including 25,600 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 0.55 (25600 hom., cov: 31)
• Consequence: METTL16 NM_024086.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL16	NM_024086.4	c.728+917A>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.728+917A>G		intron_variant	Intron 6 of 9	1	NM_024086.4	ENSP00000263092.5

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83814 AN: 151844 Hom.: 25545 Cov.: 31

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.552 AC: 83933 AN: 151962 Hom.: 25600 Cov.: 31 AF XY: 0.552 AC XY: 41009 AN XY: 74282

African (AFR) AF: 0.827 AC: 34321 AN: 41480

American (AMR) AF: 0.460 AC: 7028 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1723 AN: 3466

East Asian (EAS) AF: 0.470 AC: 2422 AN: 5156

South Asian (SAS) AF: 0.717 AC: 3445 AN: 4808

European-Finnish (FIN) AF: 0.428 AC: 4514 AN: 10554

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28769 AN: 67926

Other (OTH) AF: 0.507 AC: 1068 AN: 2106

Alfa AF: 0.456 Hom.: 30206

Bravo AF: 0.563

Asia WGS AF: 0.615 AC: 2140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.45
PhyloP100		-0.045
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: rs4268798; hg19: chr17-2366585;