2-85539315-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_005911.6(MAT2A):ā€‹c.28G>Cā€‹(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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

MAT2A
NM_005911.6 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.73
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MAT2A. . Gene score misZ 3.6313 (greater than the threshold 3.09). Trascript score misZ 4.6714 (greater than threshold 3.09). GenCC has associacion of gene with familial thoracic aortic aneurysm and aortic dissection.
BP4
Computational evidence support a benign effect (MetaRNN=0.31365967).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAT2ANM_005911.6 linkuse as main transcriptc.28G>C p.Glu10Gln missense_variant 1/9 ENST00000306434.8 NP_005902.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAT2AENST00000306434.8 linkuse as main transcriptc.28G>C p.Glu10Gln missense_variant 1/91 NM_005911.6 ENSP00000303147 P1P31153-1
MAT2AENST00000465151.5 linkuse as main transcriptn.148G>C non_coding_transcript_exon_variant 1/22
MAT2AENST00000469221.5 linkuse as main transcriptn.148G>C non_coding_transcript_exon_variant 1/32

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1453824
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
723380
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000825
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 05, 2023The 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
T
BayesDel_noAF
Benign
-0.14
CADD
Benign
23
DANN
Benign
0.91
DEOGEN2
Benign
0.20
T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.18
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
D
M_CAP
Pathogenic
0.72
D
MetaRNN
Benign
0.31
T
MetaSVM
Uncertain
0.076
D
MutationAssessor
Benign
0.97
L
MutationTaster
Benign
0.82
N
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.20
N
REVEL
Benign
0.24
Sift
Benign
0.39
T
Sift4G
Benign
0.48
T
Polyphen
0.0
B
Vest4
0.24
MutPred
0.28
Loss of helix (P = 0.1299);
MVP
0.63
MPC
1.2
ClinPred
0.37
T
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.088
gMVP
0.63

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.

Other links and lift over

dbSNP: rs748650397; hg19: chr2-85766438; API