Variant 17-2420307-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000263092.11(METTL16):c.1352A>G(p.Gln451Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000714 in 1,612,666 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 1 hom. )

Consequence

METTL16
ENST00000263092.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010703772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL16	NM_024086.4 linkuse as main transcript	c.1352A>G	p.Gln451Arg	missense_variant	10/10	ENST00000263092.11	NP_076991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL16	ENST00000263092.11 linkuse as main transcript	c.1352A>G	p.Gln451Arg	missense_variant	10/10	1	NM_024086.4	ENSP00000263092	P1	Q86W50-1
METTL16	ENST00000571669.6 linkuse as main transcript	n.1357A>G		non_coding_transcript_exon_variant	9/9	5
METTL16	ENST00000574752.5 linkuse as main transcript	c.*896A>G		3_prime_UTR_variant, NMD_transcript_variant	10/10	5		ENSP00000460207
METTL16	ENST00000576556.5 linkuse as main transcript	c.*729A>G		3_prime_UTR_variant, NMD_transcript_variant	8/8	2		ENSP00000460775

Frequencies

GnomAD3 genomes

AF:

0.000420

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000666

AC:

165

AN:

247656

Hom.:

AF XY:

0.000706

AC XY:

AN XY:

134572

show subpopulations

Gnomad AFR exome

AF:

0.000260

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.000196

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000744

AC:

1087

AN:

1460308

Hom.:

Cov.:

AF XY:

0.000793

AC XY:

576

AN XY:

726574

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000568

Gnomad4 FIN exome

AF:

0.000135

Gnomad4 NFE exome

AF:

0.000883

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000420

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000697

Hom.:

Bravo

AF:

0.000506

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000269

AC:

ESP6500EA

AF:

0.000488

AC:

ExAC

AF:

0.000902

AC:

109

EpiCase

AF:

0.000709

EpiControl

AF:

0.000830

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2023

The c.1352A>G (p.Q451R) alteration is located in exon 10 (coding exon 9) of the METTL16 gene. This alteration results from a A to G substitution at nucleotide position 1352, causing the glutamine (Q) at amino acid position 451 to be replaced by an arginine (R). 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

0.061

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0080

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.63

M_CAP

Benign

0.011

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.35

REVEL

Benign

0.048

Sift

Benign

0.044

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.030

MVP

0.22

MPC

0.33

ClinPred

0.021

GERP RS

5.3

Varity_R

0.078

gMVP

0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over