Variant 6-110358040-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001123364.3(METTL24):c.233G>A(p.Ser78Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000117 in 1,114,060 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S78T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

METTL24
NM_001123364.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

Variant links:

Genes affected

METTL24 (HGNC:21566): (methyltransferase like 24) Predicted to enable methyltransferase activity. Predicted to be involved in methylation. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

METTL24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13820988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METTL24	NM_001123364.3 linkuse as main transcript	c.233G>A	p.Ser78Asn	missense_variant	1/5	ENST00000338882.5
METTL24	NM_001354594.2 linkuse as main transcript	c.-219G>A		5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL24	ENST00000338882.5 linkuse as main transcript	c.233G>A	p.Ser78Asn	missense_variant	1/5	5	NM_001123364.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00000672

AC:

AN:

148886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000134

AC:

129

AN:

965174

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

453380

show subpopulations

Gnomad4 AFR exome

AF:

0.0000520

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:

0.000137

Gnomad4 OTH exome

AF:

0.000337

GnomAD4 genome

AF:

0.00000672

AC:

AN:

148886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72574

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

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 19, 2022

The c.233G>A (p.S78N) alteration is located in exon 1 (coding exon 1) of the METTL24 gene. This alteration results from a G to A substitution at nucleotide position 233, causing the serine (S) at amino acid position 78 to be replaced by an asparagine (N). 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

0.30

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0029

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.098

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

MutationTaster

Benign

0.94

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.080

REVEL

Benign

0.13

Sift

Benign

0.13

Sift4G

Benign

0.20

Polyphen

0.34

Vest4

0.080

MutPred

0.17

Loss of phosphorylation at S78 (P = 0.0043);

MVP

0.37

MPC

0.19

ClinPred

0.66

GERP RS

3.5

Varity_R

0.12

gMVP

0.41

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