Variant rs2302607 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024109.4(METTL22):c.655G>A(p.Ala219Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,603,568 control chromosomes in the GnomAD database, including 53,780 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3785 hom., cov: 33)

Exomes 𝑓: 0.26 ( 49995 hom. )

Consequence

METTL22
NM_024109.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.88

Variant links:

Genes affected

METTL22 (HGNC:28368): (methyltransferase 22, Kin17 lysine) This gene encodes a member of the non-histone lysine methyltransferases. It interacts with its substrate, Kin17, which is involved in DNA repair and replication and mRNA processing. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

METTL22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070168376).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL22	NM_024109.4 linkuse as main transcript	c.655G>A	p.Ala219Thr	missense_variant	5/11	ENST00000381920.8	NP_077014.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL22	ENST00000381920.8 linkuse as main transcript	c.655G>A	p.Ala219Thr	missense_variant	5/11	5	NM_024109.4	ENSP00000371345	P2	Q9BUU2-1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29771

AN:

151964

Hom.:

3785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0554

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.0934

Gnomad EAS

AF:

0.356

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.200

GnomAD3 exomes

AF:

0.223

AC:

54396

AN:

244294

Hom.:

6970

AF XY:

0.224

AC XY:

29762

AN XY:

132658

show subpopulations

Gnomad AFR exome

AF:

0.0507

Gnomad AMR exome

AF:

0.149

Gnomad ASJ exome

AF:

0.0965

Gnomad EAS exome

AF:

0.370

Gnomad SAS exome

AF:

0.164

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.255

AC:

370453

AN:

1451486

Hom.:

49995

Cov.:

AF XY:

0.253

AC XY:

182320

AN XY:

720806

show subpopulations

Gnomad4 AFR exome

AF:

0.0444

Gnomad4 AMR exome

AF:

0.154

Gnomad4 ASJ exome

AF:

0.0958

Gnomad4 EAS exome

AF:

0.347

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.276

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.196

AC:

29768

AN:

152082

Hom.:

3785

Cov.:

AF XY:

0.196

AC XY:

14567

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0555

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.0934

Gnomad4 EAS

AF:

0.356

Gnomad4 SAS

AF:

0.171

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.199

Alfa

AF:

0.250

Hom.:

9774

Bravo

AF:

0.187

TwinsUK

AF:

0.262

AC:

972

ALSPAC

AF:

0.283

AC:

1092

ESP6500AA

AF:

0.0589

AC:

240

ESP6500EA

AF:

0.255

AC:

2143

ExAC

AF:

0.223

AC:

26995

Asia WGS

AF:

0.240

AC:

834

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Benign

6.0

DANN

Uncertain

1.0

DEOGEN2

Benign

0.00085

T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.88

D;D

MetaRNN

Benign

0.0070

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.24

N;.

MutationTaster

Benign

0.98

P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

0.070

N;N

REVEL

Benign

0.013

Sift

Benign

0.62

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.012

B;.

Vest4

0.096

MPC

0.016

ClinPred

0.0088

GERP RS

-0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.44

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