Variant 1-171784117-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015935.5(METTL13):c.531G>T(p.Glu177Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

METTL13
NM_015935.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.920

Variant links:

Genes affected

METTL13 (HGNC:24248): (methyltransferase 13, eEF1A N-terminus and K55) Predicted to enable methyltransferase activity. Involved in negative regulation of cell cycle G1/S phase transition and negative regulation of transcription by RNA polymerase II. Predicted to be located in mitochondrion and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

METTL13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16892084).

BS2

High AC in GnomAd at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
METTL13	NM_015935.5 linkuse as main transcript	c.531G>T	p.Glu177Asp	missense_variant	2/8	ENST00000361735.4
METTL13	NM_014955.3 linkuse as main transcript	c.273G>T	p.Glu91Asp	missense_variant	2/8
METTL13	NM_001007239.2 linkuse as main transcript	c.453+78G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL13	ENST00000361735.4 linkuse as main transcript	c.531G>T	p.Glu177Asp	missense_variant	2/8	1	NM_015935.5	P1	Q8N6R0-5
METTL13	ENST00000367737.9 linkuse as main transcript	c.453+78G>T		intron_variant		1			Q8N6R0-1
METTL13	ENST00000362019.7 linkuse as main transcript	c.273G>T	p.Glu91Asp	missense_variant	2/8	2			Q8N6R0-3
METTL13	ENST00000485629.1 linkuse as main transcript	n.565+78G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251410

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000179

AC:

261

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

114

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000231

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Dec 03, 2021

The c.531G>T (p.E177D) alteration is located in exon 2 (coding exon 2) of the METTL13 gene. This alteration results from a G to T substitution at nucleotide position 531, causing the glutamic acid (E) at amino acid position 177 to be replaced by an aspartic acid (D). 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

0.14

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.017

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.0045

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.047

Sift

Benign

0.35

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.70

.;P

Vest4

0.42

MutPred

0.38

.;Loss of catalytic residue at W179 (P = 0.0719);

MVP

0.36

MPC

0.21

ClinPred

0.050

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.051

gMVP

0.29

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