10-80280846-A-G

Variant names:

• chr10-80280846-A-G
• rs71481597
• NM_000429.3:c.293-54T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000429.3(MAT1A):​c.293-54T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 1,296,188 control chromosomes in the GnomAD database, including 4,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (293 hom., cov: 32)
  • Exomes 𝑓: 0.078 (4023 hom.)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.459
• Publications: 3 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-80280846-A-G is Benign according to our data. Variant chr10-80280846-A-G is described in ClinVar as Benign. ClinVar VariationId is 1287609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.293-54T>C		intron_variant	Intron 3 of 8	ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.293-54T>C		intron_variant	Intron 3 of 8	1	NM_000429.3	ENSP00000361287.3
MAT1A	ENST00000455001.1	c.104-54T>C		intron_variant	Intron 2 of 4	5		ENSP00000414961.1

Frequencies

GnomAD3 genomes AF: 0.0546 AC: 8306 AN: 152158 Hom.: 293 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0475

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0510

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0832

Gnomad OTH AF: 0.0645

GnomAD4 exome AF: 0.0783 AC: 89569 AN: 1143912 Hom.: 4023 AF XY: 0.0780 AC XY: 45606 AN XY: 584546

African (AFR) AF: 0.0141 AC: 384 AN: 27254

American (AMR) AF: 0.0383 AC: 1698 AN: 44310

Ashkenazi Jewish (ASJ) AF: 0.0802 AC: 1939 AN: 24172

East Asian (EAS) AF: 0.000157 AC: 6 AN: 38238

South Asian (SAS) AF: 0.0571 AC: 4554 AN: 79790

European-Finnish (FIN) AF: 0.0550 AC: 2879 AN: 52310

Middle Eastern (MID) AF: 0.0947 AC: 493 AN: 5206

European-Non Finnish (NFE) AF: 0.0900 AC: 74090 AN: 822766

Other (OTH) AF: 0.0707 AC: 3526 AN: 49866

GnomAD4 genome AF: 0.0545 AC: 8303 AN: 152276 Hom.: 293 Cov.: 32 AF XY: 0.0525 AC XY: 3908 AN XY: 74454

African (AFR) AF: 0.0150 AC: 625 AN: 41570

American (AMR) AF: 0.0473 AC: 724 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0512 AC: 247 AN: 4820

European-Finnish (FIN) AF: 0.0489 AC: 519 AN: 10608

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0832 AC: 5656 AN: 68008

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0631 Hom.: 37

Bravo AF: 0.0545

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.90
DANN	Benign	0.37
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs71481597; hg19: chr10-82040602;