Variant chr10-80272689-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000429.3(MAT1A):c.*1092C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 152,442 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 293 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1 hom. )

Consequence

MAT1A
NM_000429.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.169

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-80272689-G-C is Benign according to our data. Variant chr10-80272689-G-C is described in ClinVar as [Benign]. Clinvar id is 301159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT1A	NM_000429.3 linkuse as main transcript	c.*1092C>G		3_prime_UTR_variant	9/9	ENST00000372213.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
MAT1A	ENST00000372213.8 linkuse as main transcript	c.*1092C>G	3_prime_UTR_variant	9/9	1	NM_000429.3	P1
MAT1A	ENST00000485270.5 linkuse as main transcript	n.1792C>G	non_coding_transcript_exon_variant	3/3	2
MAT1A	ENST00000480845.1 linkuse as main transcript	n.621-109C>G	intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0544

AC:

8280

AN:

152124

Hom.:

293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.0474

Gnomad ASJ

AF:

0.0767

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0506

Gnomad FIN

AF:

0.0487

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0830

Gnomad OTH

AF:

0.0645

GnomAD4 exome

AF:

0.0350

AC:

AN:

200

Hom.:

Cov.:

AF XY:

0.0321

AC XY:

AN XY:

156

show subpopulations

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0432

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0544

AC:

8277

AN:

152242

Hom.:

293

Cov.:

AF XY:

0.0524

AC XY:

3901

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0148

Gnomad4 AMR

AF:

0.0472

Gnomad4 ASJ

AF:

0.0767

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0509

Gnomad4 FIN

AF:

0.0487

Gnomad4 NFE

AF:

0.0830

Gnomad4 OTH

AF:

0.0639

Alfa

AF:

0.0642

Hom.:

Bravo

AF:

0.0543

Asia WGS

AF:

0.0220

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hepatic methionine adenosyltransferase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

-0.84

CADD

Benign

1.3

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over