rs752610348

Variant names:

• chr17-2420124-C-A
• NM_024086.4:c.1535G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-2420124-C-A
• chr17-2420124-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024086.4(METTL16):​c.1535G>T​(p.Gly512Val) 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. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G512A) 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

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09640694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL16	NM_024086.4	c.1535G>T	p.Gly512Val	missense_variant	Exon 10 of 10	ENST00000263092.11	NP_076991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL16	ENST00000263092.11	c.1535G>T	p.Gly512Val	missense_variant	Exon 10 of 10	1	NM_024086.4	ENSP00000263092.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.072
Sift	Benign	0.11	T
Sift4G	Benign	0.31	T
Polyphen		0.12	B
Vest4		0.21
MutPred		0.36		Gain of ubiquitination at K517 (P = 0.0828);
MVP		0.30
MPC		0.38
ClinPred		0.16	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.098
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-2323418;