17-2420123-TC-AG

Variant names:

• chr17-2420123-TC-AG
• NM_024086.4:c.1535_1536delGAinsCT
• METTL16 p.Gly512Ala

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_024086.4(METTL16):​c.1535_1536delGAinsCT​(p.Gly512Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G512R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: METTL16 NM_024086.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024086.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL16	NM_024086.4	MANE Select	c.1535_1536delGAinsCT	p.Gly512Ala	missense	N/A	NP_076991.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL16	ENST00000263092.11	TSL:1 MANE Select	c.1535_1536delGAinsCT	p.Gly512Ala	missense	N/A	ENSP00000263092.5	Q86W50-1
	METTL16	ENST00000571669.6	TSL:5	n.1540_1541delGAinsCT		non_coding_transcript_exon	Exon 9 of 9
	METTL16	ENST00000576556.5	TSL:2	n.*912_*913delGAinsCT		non_coding_transcript_exon	Exon 8 of 8	ENSP00000460775.1	I3L3W3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-2323417;