Genetic Variant MAT1A:c.*995delC (chr10-80272785-TG-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000429.3(MAT1A):c.*995delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 152,310 control chromosomes in the GnomAD database, including 998 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.099 ( 998 hom., cov: 31)

Exomes 𝑓: 0.036 ( 0 hom. )

Consequence

MAT1A
NM_000429.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.955

Publications

1 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 -10 ACMG points.

BP6

Variant 10-80272785-TG-T is Benign according to our data. Variant chr10-80272785-TG-T is described in ClinVar as [Benign]. Clinvar id is 301164.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3 link	c.*995delC		3_prime_UTR_variant	Exon 9 of 9	ENST00000372213.8	NP_000420.1	Q00266

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAT1A	ENST00000372213.8 link	c.*995delC	3_prime_UTR_variant	Exon 9 of 9	1	NM_000429.3	ENSP00000361287.3	Q00266
MAT1A	ENST00000485270.5 link	n.1695delC	non_coding_transcript_exon_variant	Exon 3 of 3	2
MAT1A	ENST00000480845.1 link	n.621-206delC	intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.0990

AC:

15050

AN:

152084

Hom.:

989

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0304

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.0174

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.0720

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.112

GnomAD4 exome

AF:

0.0364

AC:

AN:

110

Hom.:

Cov.:

AF XY:

0.0455

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0444

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0990

AC:

15074

AN:

152200

Hom.:

998

Cov.:

AF XY:

0.100

AC XY:

7458

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0303

AC:

1258

AN:

41530

American (AMR)

AF:

0.190

AC:

2906

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

351

AN:

3470

East Asian (EAS)

AF:

0.0174

AC:

AN:

5174

South Asian (SAS)

AF:

0.243

AC:

1175

AN:

4832

European-Finnish (FIN)

AF:

0.0720

AC:

763

AN:

10596

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.121

AC:

8231

AN:

67990

Other (OTH)

AF:

0.116

AC:

245

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

663

1326

1988

2651

3314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0476

Hom.:

Bravo

AF:

0.102

Asia WGS

AF:

0.145

AC:

505

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hepatic methionine adenosyltransferase deficiency

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.95

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

10-80272785-TG-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over