Variant chr16-21599767-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016025.5(METTL9):c.34C>G(p.Leu12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

METTL9
NM_016025.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.291

Variant links:

Genes affected

METTL9 (HGNC:24586): (methyltransferase 9, His-X-His N1(pi)-histidine) Enables protein-L-histidine N-pros-methyltransferase activity. Predicted to be involved in methylation. Is active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

METTL9 links:

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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=0.057032347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
METTL9	NM_016025.5 linkuse as main transcript	c.34C>G	p.Leu12Val	missense_variant	1/5	ENST00000358154.8
METTL9	NM_001077180.3 linkuse as main transcript	c.34C>G	p.Leu12Val	missense_variant	1/5
METTL9	NM_001288659.2 linkuse as main transcript	c.45+2467C>G		intron_variant
METTL9	NM_001288660.2 linkuse as main transcript	c.45+2467C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL9	ENST00000358154.8 linkuse as main transcript	c.34C>G	p.Leu12Val	missense_variant	1/5	1	NM_016025.5	P3	Q9H1A3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000617

AC:

AN:

161988

Hom.:

AF XY:

0.0000109

AC XY:

AN XY:

91618

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.000269

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.000276

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000854

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.13

M_CAP

Benign

0.069

MetaRNN

Benign

0.057

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.11

N;N

MutationTaster

Benign

0.67

N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.037

Sift

Benign

0.25

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.0

B;B

Vest4

0.098

MVP

0.37

MPC

0.91

ClinPred

0.056

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over