17-2477734-C-T

Position:

• chr17-2477734-C-T

Variant summary

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

The NM_024086.4(METTL16):​c.280G>A​(p.Gly94Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: METTL16 NM_024086.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.90

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]

METTL16 (HGNC:):

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=0.23457947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL16	NM_024086.4	c.280G>A	p.Gly94Ser	missense_variant	3/10	ENST00000263092.11	NP_076991.3
METTL16	XM_047436697.1	c.-129G>A		5_prime_UTR_variant	2/9		XP_047292653.1
METTL16	XR_007065448.1	n.410G>A		non_coding_transcript_exon_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL16	ENST00000263092.11	c.280G>A	p.Gly94Ser	missense_variant	3/10	1	NM_024086.4	ENSP00000263092.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461656 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.280G>A (p.G94S) alteration is located in exon 3 (coding exon 2) of the METTL16 gene. This alteration results from a G to A substitution at nucleotide position 280, causing the glycine (G) at amino acid position 94 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	0.092
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.32	N;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.2	N;.
REVEL	Benign	0.13
Sift	Benign	0.092	T;.
Sift4G	Benign	0.29	T;T
Polyphen		0.66	P;.
Vest4		0.31
MutPred		0.46		Gain of disorder (P = 0.056);Gain of disorder (P = 0.056);
MVP		0.15
MPC		1.5
ClinPred		0.51	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-2381028; COSMIC: COSV99563839;