10-80272760-G-T

Variant names:

• chr10-80272760-G-T
• rs886047310
• NM_000429.3:c.*1021C>A

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_000429.3(MAT1A):c.*1021C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The gene MAT1A is a tumor suppressor gene (CancerMine: 8 TSG, 2 oncogene, 2 driver citations). The gene MAT1A is a known oncogene (CancerMine: 8 TSG, 2 oncogene, 2 driver citations). The gene MAT1A is a cancer driver gene (CancerMine: 8 TSG, 2 oncogene, 2 driver citations). The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAT1A NM_000429.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• Publications: 0 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: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000429.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MAT1A NM_000429.3	MANE Select	c.*1021C>A	3_prime_UTR	Exon 9 of 9	Prot: NP_000420.1 UniProt:

MAT1A NM_000429.3

MANE Select

HGVSc / HGVSpc.*1021C>A

Exon rankExon 9 of 9

3_prime_UTR

Prot: NP_000420.1UniProt: Q00266

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MAT1A ENST00000372213.8	TSL:1MANE Select	c.*1021C>A	3_prime_UTR	Exon 9 of 9	Prot: ENSP00000361287.3 UniProt:
	MAT1A ENST00000871627.1		c.*1021C>A	3_prime_UTR	Exon 9 of 9	Prot: ENSP00000541686.1 UniProt:
	MAT1A ENST00000871624.1		c.*1021C>A	3_prime_UTR	Exon 9 of 9	Prot: ENSP00000541683.1 UniProt:

MAT1A ENST00000372213.8

TSL:1MANE Select

HGVSc / HGVSpc.*1021C>A

Exon rankExon 9 of 9

3_prime_UTR

Prot: ENSP00000361287.3UniProt: Q00266

MAT1A ENST00000871627.1

HGVSc / HGVSpc.*1021C>A

Exon rankExon 9 of 9

3_prime_UTR

Prot: ENSP00000541686.1UniProt: A0ACI8QDF3

MAT1A ENST00000871624.1

HGVSc / HGVSpc.*1021C>A

Exon rankExon 9 of 9

3_prime_UTR

Prot: ENSP00000541683.1UniProt: A0ACI8PRD3

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 exome Warning	AF: 0.00	AC:0	Hom:0	AN:124	Cov:0
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	2.4
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.74
GPN-Star LLR	N/A	0.18
GPN-Star score	N/A	-0.18
PhyloP100	Benign	0.14

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs886047310;

hg19: chr10-82032516;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar