rs776303477

Variant names:

• chr2-85539326-C-G
• rs776303477
• NM_005911.6:c.39C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-85539326-C-G
• chr2-85539326-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005911.6(MAT2A):​c.39C>G​(p.Ile13Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. I13V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAT2A NM_005911.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.170
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.39C>G	p.Ile13Met	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.39C>G	p.Ile13Met	missense	Exon 1 of 9	ENSP00000303147.3	P31153-1
	MAT2A	ENST00000881374.1		c.39C>G	p.Ile13Met	missense	Exon 1 of 9	ENSP00000551433.1
	MAT2A	ENST00000881376.1		c.39C>G	p.Ile13Met	missense	Exon 1 of 9	ENSP00000551435.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.55
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.17
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	0.64	N
REVEL	Uncertain	0.46
Sift	Benign	0.71	T
Sift4G	Benign	0.82	T
Polyphen		0.0040	B
Vest4		0.56
MutPred		0.70		Gain of disorder (P = 0.0303)
MVP		0.92
MPC		1.4
ClinPred		0.29	T
GERP RS		1.8
PromoterAI		-0.078	Neutral
Varity_R		0.16
gMVP		0.71
Mutation Taster		=73/27	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: rs776303477; hg19: chr2-85766449;