rs11595587

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000429.3(MAT1A):c.-153C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 694,976 control chromosomes in the GnomAD database, including 340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 77 hom., cov: 32)

Exomes 𝑓: 0.028 ( 263 hom. )

Consequence

MAT1A
NM_000429.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.127

Publications

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

MAT1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 10-80289576-G-A is Benign according to our data. Variant chr10-80289576-G-A is described in ClinVar as Benign. ClinVar VariationId is 301205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0247 (3757/152120) while in subpopulation NFE AF = 0.0365 (2485/68000). AF 95% confidence interval is 0.0353. There are 77 homozygotes in GnomAd4. There are 1828 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 77 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3 link	c.-153C>T		5_prime_UTR_variant	Exon 1 of 9	ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8 link	c.-153C>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_000429.3	ENSP00000361287.3
MAT1A	ENST00000455001.1 link	c.-219C>T		upstream_gene_variant		5		ENSP00000414961.1

Frequencies

GnomAD3 genomes

AF:

0.0247

AC:

3754

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00611

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.0248

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0426

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0365

Gnomad OTH

AF:

0.0244

GnomAD4 exome

AF:

0.0278

AC:

15075

AN:

542856

Hom.:

263

Cov.:

AF XY:

0.0266

AC XY:

7811

AN XY:

294154

show subpopulations

African (AFR)

AF:

0.00810

AC:

125

AN:

15426

American (AMR)

AF:

0.0219

AC:

747

AN:

34118

Ashkenazi Jewish (ASJ)

AF:

0.0212

AC:

412

AN:

19460

East Asian (EAS)

AF:

0.00

AC:

AN:

31608

South Asian (SAS)

AF:

0.00648

AC:

400

AN:

61694

European-Finnish (FIN)

AF:

0.0384

AC:

1342

AN:

34976

Middle Eastern (MID)

AF:

0.0221

AC:

AN:

2802

European-Non Finnish (NFE)

AF:

0.0358

AC:

11214

AN:

313014

Other (OTH)

AF:

0.0260

AC:

773

AN:

29758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

835

1670

2504

3339

4174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.0247

AC:

3757

AN:

152120

Hom.:

Cov.:

AF XY:

0.0246

AC XY:

1828

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00610

AC:

253

AN:

41498

American (AMR)

AF:

0.0248

AC:

379

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00456

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0426

AC:

450

AN:

10566

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0365

AC:

2485

AN:

68000

Other (OTH)

AF:

0.0242

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

181

362

542

723

904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0326

Hom.:

366

Bravo

AF:

0.0231

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hepatic methionine adenosyltransferase deficiency

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.1

(source)

DANN

Benign

0.85

PhyloP100

-0.13

PromoterAI

0.025

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over