Variant 14-20992611-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000339374.11(METTL17):c.517G>T(p.Ala173Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00842 in 1,613,642 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0061 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0087 ( 84 hom. )

Consequence

METTL17
ENST00000339374.11 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.49

Variant links:

Genes affected

METTL17 (HGNC:19280): (methyltransferase like 17) Predicted to enable S-adenosyl-L-methionine binding activity and mitochondrial ribosome binding activity. Predicted to be involved in ribosomal small subunit biogenesis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

METTL17 links:

METTL17 (HGNC:):

METTL17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0094872415).

BP6

Variant 14-20992611-G-T is Benign according to our data. Variant chr14-20992611-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2644055.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL17	NM_022734.3 linkuse as main transcript	c.517G>T	p.Ala173Ser	missense_variant	5/14	ENST00000339374.11	NP_073571.1	Q9H7H0-1A0A0S2Z5L8
METTL17	NM_001029991.2 linkuse as main transcript	c.517G>T	p.Ala173Ser	missense_variant	5/13		NP_001025162.1	Q9H7H0-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL17	ENST00000339374.11 linkuse as main transcript	c.517G>T	p.Ala173Ser	missense_variant	5/14	1	NM_022734.3	ENSP00000343041.6		Q9H7H0-1

Frequencies

GnomAD3 genomes

AF:

0.00612

AC:

931

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00867

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00694

AC:

1744

AN:

251450

Hom.:

AF XY:

0.00692

AC XY:

940

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.0325

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00314

Gnomad FIN exome

AF:

0.00471

Gnomad NFE exome

AF:

0.00935

Gnomad OTH exome

AF:

0.00635

GnomAD4 exome

AF:

0.00866

AC:

12648

AN:

1461324

Hom.:

Cov.:

AF XY:

0.00855

AC XY:

6216

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00271

Gnomad4 ASJ exome

AF:

0.0324

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00335

Gnomad4 FIN exome

AF:

0.00434

Gnomad4 NFE exome

AF:

0.00946

Gnomad4 OTH exome

AF:

0.00931

GnomAD4 genome

AF:

0.00611

AC:

931

AN:

152318

Hom.:

Cov.:

AF XY:

0.00618

AC XY:

460

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.00601

Gnomad4 ASJ

AF:

0.0277

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00490

Gnomad4 NFE

AF:

0.00867

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00922

Hom.:

Bravo

AF:

0.00595

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0119

AC:

102

ExAC

AF:

0.00677

AC:

822

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00878

EpiControl

AF:

0.00853

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

METTL17: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;.;.;.;T;T

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

D;D;D;D;T;D

MetaRNN

Benign

0.0095

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M;M;.;.;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.7

N;N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.059

T;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0

D;D;D;.;.;.

Vest4

0.67

MVP

0.49

MPC

0.93

ClinPred

0.023

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.66

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