Variant 2-171331809-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_001321154.2(METTL8):c.715G>A(p.Val239Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,603,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

METTL8
NM_001321154.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.56

Variant links:

Genes affected

METTL8 (HGNC:25856): (methyltransferase 8, tRNA N3-cytidine) Enables mRNA methyltransferase activity. Involved in mRNA methylation. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

METTL8 links:

METTL8 (HGNC:):

METTL8 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=0.034466863).

BP6

Variant 2-171331809-C-T is Benign according to our data. Variant chr2-171331809-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2225166.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL8	NM_001321154.2 linkuse as main transcript	c.715G>A	p.Val239Ile	missense_variant	6/10	ENST00000375258.9	NP_001308083.1	Q9H825B3KW44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL8	ENST00000375258.9 linkuse as main transcript	c.715G>A	p.Val239Ile	missense_variant	6/10	5	NM_001321154.2	ENSP00000364407.4		B3KW44

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000588

AC:

AN:

237912

Hom.:

AF XY:

0.0000313

AC XY:

AN XY:

127922

show subpopulations

Gnomad AFR exome

AF:

0.000134

Gnomad AMR exome

AF:

0.0000910

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000952

Gnomad NFE exome

AF:

0.0000465

Gnomad OTH exome

AF:

0.000338

GnomAD4 exome

AF:

0.0000317

AC:

AN:

1450786

Hom.:

Cov.:

AF XY:

0.0000250

AC XY:

AN XY:

720670

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.0000461

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000756

Gnomad4 NFE exome

AF:

0.0000253

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000907

AC:

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

Apr 13, 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

0.10

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.025

.;T;.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.71

T;T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.034

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;.;.;L

MutationTaster

Benign

0.97

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.47

.;N;.;.

REVEL

Benign

0.031

Sift

Benign

0.16

.;T;.;.

Sift4G

Benign

0.19

T;T;.;.

Polyphen

0.19

B;.;.;P

Vest4

0.26

MVP

0.014

MPC

0.097

ClinPred

0.026

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.025

gMVP

0.42

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