NM_005911.6:c.28G>C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005911.6(MAT2A):c.28G>C(p.Glu10Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. E10D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MAT2A
NM_005911.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.73

Publications

0 publications found

Variant links:

Genes affected

MAT2A (HGNC:6904): (methionine adenosyltransferase 2A) The protein encoded by this gene catalyzes the production of S-adenosylmethionine (AdoMet) from methionine and ATP. AdoMet is the key methyl donor in cellular processes. [provided by RefSeq, Jun 2011]

MAT2A links:

PARTICL (HGNC:50886): (promoter of MAT2A antisense radiation-induced circulating long non-coding RNA)

PARTICL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31365967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2A	NM_005911.6 link	c.28G>C	p.Glu10Gln	missense_variant	Exon 1 of 9	ENST00000306434.8	NP_005902.1	P31153-1A0A140VJP5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAT2A	ENST00000306434.8 link	c.28G>C	p.Glu10Gln	missense_variant	Exon 1 of 9	1	NM_005911.6	ENSP00000303147.3	P31153-1
MAT2A	ENST00000465151.5 link	n.148G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
MAT2A	ENST00000469221.5 link	n.148G>C		non_coding_transcript_exon_variant	Exon 1 of 3	2
PARTICL	ENST00000667933.3 link	n.-205C>G		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000413

AC:

AN:

241854

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000908

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453824

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723380

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32356

American (AMR)

AF:

0.00

AC:

AN:

43952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25850

East Asian (EAS)

AF:

0.00

AC:

AN:

38492

South Asian (SAS)

AF:

0.00

AC:

AN:

85310

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108800

Other (OTH)

AF:

0.00

AC:

AN:

60022

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cardiovascular phenotype

Uncertain:1

Sep 05, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.E10Q variant (also known as c.28G>C), located in coding exon 1 of the MAT2A gene, results from a G to C substitution at nucleotide position 28. The glutamic acid at codon 10 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.20

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.18

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.31

MetaSVM

Uncertain

0.076

MutationAssessor

Benign

0.97

PhyloP100

4.7

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.20

REVEL

Benign

0.24

Sift

Benign

0.39

Sift4G

Benign

0.48

Polyphen

0.0

Vest4

0.24

MutPred

0.28

Loss of helix (P = 0.1299);

MVP

0.63

MPC

1.2

ClinPred

0.37

GERP RS

3.8

PromoterAI

0.051

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.088

gMVP

0.63

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over