Variant 17-2420170-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024086.4(METTL16):c.1489G>A(p.Gly497Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000774 in 1,614,224 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

METTL16
NM_024086.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.20

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:

METTL16 (HGNC:):

METTL16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0075424314).

BP6

Variant 17-2420170-C-T is Benign according to our data. Variant chr17-2420170-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2362858.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL16	NM_024086.4 linkuse as main transcript	c.1489G>A	p.Gly497Ser	missense_variant	10/10	ENST00000263092.11	NP_076991.3	Q86W50-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL16	ENST00000263092.11 linkuse as main transcript	c.1489G>A	p.Gly497Ser	missense_variant	10/10	1	NM_024086.4	ENSP00000263092.5		Q86W50-1

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000104

AC:

AN:

249582

Hom.:

AF XY:

0.0000739

AC XY:

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.00116

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000417

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.0000894

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:

0.0000243

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000420

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000294

Hom.:

Bravo

AF:

0.000484

ESP6500AA

AF:

0.00101

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000993

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.25

DANN

Benign

0.73

DEOGEN2

Benign

0.0080

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.22

M_CAP

Benign

0.0073

MetaRNN

Benign

0.0075

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.55

PrimateAI

Benign

0.29

PROVEAN

Benign

0.51

REVEL

Benign

0.016

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.040

MVP

0.14

MPC

0.29

ClinPred

0.0045

GERP RS

-3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.11

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

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