chr17-2452223-A-C

Position:

• chr17-2452223-A-C

Variant summary

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

The NM_024086.4(METTL16):​c.729-10664T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 152,198 control chromosomes in the GnomAD database, including 448 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 0.065 (448 hom., cov: 32)
• Consequence: METTL16 NM_024086.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METTL16	NM_024086.4	c.729-10664T>G		intron_variant		ENST00000263092.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL16	ENST00000263092.11	c.729-10664T>G		intron_variant		1	NM_024086.4	P1
METTL16	ENST00000574752.5	c.*106-10664T>G		intron_variant, NMD_transcript_variant		5
METTL16	ENST00000576556.5	c.*106-10664T>G		intron_variant, NMD_transcript_variant		2
METTL16	ENST00000571669.6	n.734-10664T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0654 AC: 9941 AN: 152086 Hom.: 448 Cov.: 32

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0647

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0423

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0694

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

GnomAD4 genome AF: 0.0653 AC: 9939 AN: 152198 Hom.: 448 Cov.: 32 AF XY: 0.0620 AC XY: 4616 AN XY: 74414

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.0647

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0415

Gnomad4 FIN AF: 0.0473

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0931 Hom.: 990

Bravo AF: 0.0623

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs11871981; hg19: chr17-2355517;