Variant chr16-8628915-A-C 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_024109.4(METTL22):c.319A>C(p.Thr107Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,613,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

METTL22
NM_024109.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.933

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 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=0.03601393).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL22	NM_024109.4 linkuse as main transcript	c.319A>C	p.Thr107Pro	missense_variant	3/11	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.319A>C	p.Thr107Pro	missense_variant	3/11	5	NM_024109.4	ENSP00000371345	P2	Q9BUU2-1
METTL22	ENST00000163678.11 linkuse as main transcript	c.319A>C	p.Thr107Pro	missense_variant, NMD_transcript_variant	3/10	1		ENSP00000163678		Q9BUU2-2
METTL22	ENST00000561758.5 linkuse as main transcript	c.280+39A>C		intron_variant		5		ENSP00000457152	A2
METTL22	ENST00000567295.5 linkuse as main transcript	c.*5A>C		3_prime_UTR_variant, NMD_transcript_variant	3/5	3		ENSP00000457913

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.000323

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000237

AC:

AN:

249404

Hom.:

AF XY:

0.000259

AC XY:

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000433

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000240

AC:

351

AN:

1461842

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

181

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000290

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000184

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000263

Hom.:

Bravo

AF:

0.000223

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000477

AC:

ExAC

AF:

0.000207

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000415

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

Feb 15, 2023

The c.319A>C (p.T107P) alteration is located in exon 3 (coding exon 2) of the METTL22 gene. This alteration results from a A to C substitution at nucleotide position 319, causing the threonine (T) at amino acid position 107 to be replaced by a proline (P). 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

0.067

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.24

DANN

Benign

0.91

DEOGEN2

Benign

0.0034

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.31

M_CAP

Benign

0.0039

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.82

REVEL

Benign

0.073

Sift

Benign

0.032

Sift4G

Benign

0.26

Polyphen

0.0020

Vest4

0.10

MVP

0.067

MPC

0.016

ClinPred

0.046

GERP RS

-8.4

Varity_R

0.13

gMVP

0.17

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