Genetic Variant MAT1A:c.*1206G>A (chr10-80272575-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000429.3(MAT1A):c.*1206G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,390 control chromosomes in the GnomAD database, including 3,501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3499 hom., cov: 32)

Exomes 𝑓: 0.14 ( 2 hom. )

Consequence

MAT1A
NM_000429.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.32

Publications

11 publications found

Variant links:

Genes affected

MAT1A (HGNC:6903): (methionine adenosyltransferase 1A) This gene catalyzes a two-step reaction that involves the transfer of the adenosyl moiety of ATP to methionine to form S-adenosylmethionine and tripolyphosphate, which is subsequently cleaved to PPi and Pi. S-adenosylmethionine is the source of methyl groups for most biological methylations. The encoded protein is found as a homotetramer (MAT I) or a homodimer (MAT III) whereas a third form, MAT II (gamma), is encoded by the MAT2A gene. Mutations in this gene are associated with methionine adenosyltransferase deficiency. [provided by RefSeq, Jul 2008]

MAT1A Gene-Disease associations (from GenCC):

methionine adenosyltransferase deficiency
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

MAT1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 10-80272575-C-T is Benign according to our data. Variant chr10-80272575-C-T is described in ClinVar as Benign. ClinVar VariationId is 301158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000429.3. 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
	MAT1A	NM_000429.3	MANE Select	c.*1206G>A		3_prime_UTR	Exon 9 of 9	NP_000420.1	Q00266

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAT1A	ENST00000372213.8	TSL:1 MANE Select	c.*1206G>A	3_prime_UTR	Exon 9 of 9	ENSP00000361287.3	Q00266
MAT1A	ENST00000871627.1		c.*1206G>A	3_prime_UTR	Exon 9 of 9	ENSP00000541686.1
MAT1A	ENST00000871624.1		c.*1206G>A	3_prime_UTR	Exon 9 of 9	ENSP00000541683.1

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31274

AN:

151962

Hom.:

3482

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.0183

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.216

GnomAD4 exome

AF:

0.139

AC:

AN:

310

Hom.:

Cov.:

AF XY:

0.136

AC XY:

AN XY:

228

show subpopulations

African (AFR)

AF:

0.125

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.133

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.135

AC:

AN:

230

Other (OTH)

AF:

0.143

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.206

AC:

31326

AN:

152080

Hom.:

3499

Cov.:

AF XY:

0.205

AC XY:

15252

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.260

AC:

10782

AN:

41422

American (AMR)

AF:

0.269

AC:

4108

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

862

AN:

3472

East Asian (EAS)

AF:

0.0184

AC:

AN:

5176

South Asian (SAS)

AF:

0.288

AC:

1389

AN:

4824

European-Finnish (FIN)

AF:

0.134

AC:

1419

AN:

10602

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.178

AC:

12100

AN:

67990

Other (OTH)

AF:

0.218

AC:

461

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1240

2480

3721

4961

6201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.187

Hom.:

10458

Bravo

AF:

0.215

Asia WGS

AF:

0.182

AC:

636

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hepatic methionine adenosyltransferase deficiency (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.41

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.27

Position offset: 5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over