rs760251833

Variant names:

• chr2-85539324-A-G
• rs760251833
• NM_005911.6:c.37A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-85539324-A-G
• chr2-85539324-A-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4 BS2

The NM_005911.6(MAT2A):​c.37A>G​(p.Ile13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. I13M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MAT2A NM_005911.6 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.52
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36866945).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005911.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2A	NM_005911.6	MANE Select	c.37A>G	p.Ile13Val	missense	Exon 1 of 9	NP_005902.1	P31153-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2A	ENST00000306434.8	TSL:1 MANE Select	c.37A>G	p.Ile13Val	missense	Exon 1 of 9	ENSP00000303147.3	P31153-1
	MAT2A	ENST00000881374.1		c.37A>G	p.Ile13Val	missense	Exon 1 of 9	ENSP00000551433.1
	MAT2A	ENST00000881376.1		c.37A>G	p.Ile13Val	missense	Exon 1 of 9	ENSP00000551435.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000165 AC: 4 AN: 243084 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000898

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1454742 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 723814

African (AFR) AF: 0.00 AC: 0 AN: 32450

American (AMR) AF: 0.0000681 AC: 3 AN: 44052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25888

East Asian (EAS) AF: 0.00 AC: 0 AN: 38672

South Asian (SAS) AF: 0.00 AC: 0 AN: 85410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109124

Other (OTH) AF: 0.0000167 AC: 1 AN: 60050

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Cardiovascular phenotype (1)
-	1	-	Familial thoracic aortic aneurysm and aortic dissection (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	0.000035	T
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.053
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.57	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	0.31	D
MutationAssessor	Benign	0.55	N
PhyloP100		3.5
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.16	N
REVEL	Uncertain	0.35
Sift	Benign	0.64	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.51
MutPred		0.52		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.77
MPC		1.0
ClinPred		0.19	T
GERP RS		4.7
PromoterAI		0.0098	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.61
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs760251833; hg19: chr2-85766447;