rs779310038

Variant names:

• chr2-85539304-A-G
• rs779310038
• NM_005911.6:c.17A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-85539304-A-G
• chr2-85539304-A-T

Variant summary

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

The NM_005911.6(MAT2A):​c.17A>G​(p.Asn6Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,276 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N6H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAT2A NM_005911.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.11
• Publications: 1 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2A	NM_005911.6	c.17A>G	p.Asn6Ser	missense_variant	Exon 1 of 9	ENST00000306434.8	NP_005902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2A	ENST00000306434.8	c.17A>G	p.Asn6Ser	missense_variant	Exon 1 of 9	1	NM_005911.6	ENSP00000303147.3
MAT2A	ENST00000465151.5	n.137A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2
MAT2A	ENST00000469221.5	n.137A>G		non_coding_transcript_exon_variant	Exon 1 of 3	2
PARTICL	ENST00000667933.3	n.-194T>C		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000124 AC: 3 AN: 241122 AF XY: 0.00000762

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: 0.0000273

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453276 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723122

African (AFR) AF: 0.00 AC: 0 AN: 32286

American (AMR) AF: 0.00 AC: 0 AN: 43884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25836

East Asian (EAS) AF: 0.00 AC: 0 AN: 38478

South Asian (SAS) AF: 0.00 AC: 0 AN: 85200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108566

Other (OTH) AF: 0.00 AC: 0 AN: 59982

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

ExAC AF: 0.00000825 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Uncertain:1

Aug 23, 2020

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces asparagine with serine at codon 6 of the MAT2A protein (p.Asn6Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant has not been reported in the literature in individuals with MAT2A-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.063
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.74	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Benign	1.0	L
PhyloP100		8.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.64	N
REVEL	Uncertain	0.44
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.056	T
Polyphen		0.14	B
Vest4		0.54
MutPred		0.40		Gain of glycosylation at N6 (P = 0.0096);
MVP		0.71
MPC		0.98
ClinPred		0.76	D
GERP RS		4.7
PromoterAI		-0.078	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.098
gMVP		0.89
Mutation Taster		=78/22	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: rs779310038; hg19: chr2-85766427;