17-2420349-C-A

Variant names:

• chr17-2420349-C-A
• rs201182820
• NM_024086.4:c.1310G>T

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.1310G>T​(p.Arg437Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,550 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R437W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: METTL16 NM_024086.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604
• 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=0.039649665).

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.1310G>T	p.Arg437Leu	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.1310G>T	p.Arg437Leu	missense	Exon 10 of 10	ENSP00000263092.5	Q86W50-1
	METTL16	ENST00000571669.6	TSL:5	n.1315G>T		non_coding_transcript_exon	Exon 9 of 9
	METTL16	ENST00000574752.5	TSL:5	n.*854G>T		non_coding_transcript_exon	Exon 10 of 10	ENSP00000460207.1	I3L362

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459550 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.013
DANN	Benign	0.59
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.60
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.032
Sift	Benign	0.85	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.057
MutPred		0.16		Loss of loop (P = 0.0203)
MVP		0.068
MPC		0.35
ClinPred		0.026	T
GERP RS		-9.9
Varity_R		0.022
gMVP		0.17

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: rs201182820; hg19: chr17-2323643; COSMIC: COSV54012688; COSMIC: COSV54012688;