17-2420131-C-G

Variant names:

• chr17-2420131-C-G
• NM_024086.4:c.1528G>C
• METTL16 p.Val510Leu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024086.4(METTL16):​c.1528G>C​(p.Val510Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: METTL16 NM_024086.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04225418).

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.1528G>C	p.Val510Leu	missense	Exon 10 of 10	NP_076991.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL16	ENST00000263092.11	TSL:1 MANE Select	c.1528G>C	p.Val510Leu	missense	Exon 10 of 10	ENSP00000263092.5	Q86W50-1
	METTL16	ENST00000571669.6	TSL:5	n.1533G>C		non_coding_transcript_exon	Exon 9 of 9
	METTL16	ENST00000576556.5	TSL:2	n.*905G>C		non_coding_transcript_exon	Exon 8 of 8	ENSP00000460775.1	I3L3W3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.4
DANN	Benign	0.87
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.32
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.012
Sift	Benign	0.073	T
Sift4G	Benign	0.17	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.030
gMVP		0.19

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

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

Other links and lift over

hg19: chr17-2323425;