NM_024086.4:c.-1+504A>G

Variant names:

• chr17-2511255-T-C
• rs935134
• NM_024086.4:c.-1+504A>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.-1+504A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 151,846 control chromosomes in the GnomAD database, including 1,712 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 0.13 (1712 hom., cov: 30)
• Consequence: METTL16 NM_024086.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL16	NM_024086.4	c.-1+504A>G		intron_variant	Intron 1 of 9	ENST00000263092.11	NP_076991.3
METTL16	XM_047436697.1	c.-281+504A>G		intron_variant	Intron 1 of 8		XP_047292653.1
METTL16	XR_007065448.1	n.130+504A>G		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL16	ENST00000263092.11	c.-1+504A>G		intron_variant	Intron 1 of 9	1	NM_024086.4	ENSP00000263092.5

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19780 AN: 151730 Hom.: 1710 Cov.: 30

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.130 AC: 19801 AN: 151846 Hom.: 1712 Cov.: 30 AF XY: 0.136 AC XY: 10102 AN XY: 74192

African (AFR) AF: 0.0561 AC: 2325 AN: 41450

American (AMR) AF: 0.247 AC: 3770 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3470

East Asian (EAS) AF: 0.343 AC: 1765 AN: 5146

South Asian (SAS) AF: 0.209 AC: 1006 AN: 4804

European-Finnish (FIN) AF: 0.170 AC: 1779 AN: 10484

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8225 AN: 67942

Other (OTH) AF: 0.148 AC: 312 AN: 2110

Alfa AF: 0.130 Hom.: 2449

Bravo AF: 0.134

Asia WGS AF: 0.283 AC: 984 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	9.9
DANN	Benign	0.87
PhyloP100		0.52
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: rs935134; hg19: chr17-2414549;