Genetic Variant NM_005911.6:c.-129C>G (chr2-85539159-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_005911.6(MAT2A):c.-129C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 684,296 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.021 ( 60 hom., cov: 33)

Exomes 𝑓: 0.024 ( 202 hom. )

Consequence

MAT2A
NM_005911.6 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.207

Publications

3 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0213 (3248/152134) while in subpopulation NFE AF = 0.0326 (2213/67974). AF 95% confidence interval is 0.0314. There are 60 homozygotes in GnomAd4. There are 1578 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 3248 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2A	NM_005911.6 link	c.-129C>G		upstream_gene_variant		ENST00000306434.8	NP_005902.1	P31153-1A0A140VJP5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MAT2A	ENST00000306434.8 link	c.-129C>G	upstream_gene_variant	1	NM_005911.6	ENSP00000303147.3	P31153-1
MAT2A	ENST00000465151.5 link	n.-9C>G	upstream_gene_variant	2
MAT2A	ENST00000469221.5 link	n.-9C>G	upstream_gene_variant	2
PARTICL	ENST00000667933.3 link	n.-49G>C	upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3248

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00633

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0308

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00973

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.0449

Gnomad NFE

AF:

0.0326

Gnomad OTH

AF:

0.0335

GnomAD4 exome

AF:

0.0241

AC:

12805

AN:

532162

Hom.:

202

Cov.:

AF XY:

0.0237

AC XY:

6666

AN XY:

281224

show subpopulations

African (AFR)

AF:

0.00625

AC:

AN:

11360

American (AMR)

AF:

0.0212

AC:

465

AN:

21908

Ashkenazi Jewish (ASJ)

AF:

0.0152

AC:

218

AN:

14348

East Asian (EAS)

AF:

0.00

AC:

AN:

25634

South Asian (SAS)

AF:

0.0105

AC:

521

AN:

49598

European-Finnish (FIN)

AF:

0.0130

AC:

559

AN:

43154

Middle Eastern (MID)

AF:

0.0349

AC:

AN:

2380

European-Non Finnish (NFE)

AF:

0.0303

AC:

10198

AN:

336284

Other (OTH)

AF:

0.0251

AC:

690

AN:

27496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

591

1182

1774

2365

2956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0213

AC:

3248

AN:

152134

Hom.:

Cov.:

AF XY:

0.0212

AC XY:

1578

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.00633

AC:

263

AN:

41522

American (AMR)

AF:

0.0308

AC:

470

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00932

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0104

AC:

110

AN:

10602

Middle Eastern (MID)

AF:

0.0517

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0326

AC:

2213

AN:

67974

Other (OTH)

AF:

0.0331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

163

325

488

650

813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00624

Hom.:

Bravo

AF:

0.0213

Asia WGS

AF:

0.00520

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.8

(source)

DANN

Benign

0.66

PhyloP100

0.21

PromoterAI

-0.074

Neutral

(source)

Splicing

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over