NM_000429.3:c.*1021C>T

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACMG Germline Pathogenicity v2019). BP4_Strong

The NM_000429.3(MAT1A):c.*1021C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant has a gnomAD grpmax filtering allele frequency (95% CI) of 0.000193, indicating it is observed in the general population. Note: a gnomAD entry for this variant shows a statistical allele-bias signature, consistent with mosaic/somatic contamination (e.g. age-related clonal hematopoiesis) rather than true inherited population frequency — this frequency should not be read as evidence of a common, benign germline variant. 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: 𝑓 0.0000066 (0 hom., 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 ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

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>T	3_prime_UTR	Exon 9 of 9	Prot: NP_000420.1 UniProt:

MAT1A NM_000429.3

MANE Select

HGVSc / HGVSpc.*1021C>T

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>T	3_prime_UTR	Exon 9 of 9	Prot: ENSP00000361287.3 UniProt:
	MAT1A ENST00000871627.1		c.*1021C>T	3_prime_UTR	Exon 9 of 9	Prot: ENSP00000541686.1 UniProt:
	MAT1A ENST00000871624.1		c.*1021C>T	3_prime_UTR	Exon 9 of 9	Prot: ENSP00000541683.1 UniProt:

MAT1A ENST00000372213.8

TSL:1MANE Select

HGVSc / HGVSpc.*1021C>T

Exon rankExon 9 of 9

3_prime_UTR

Prot: ENSP00000361287.3UniProt: Q00266

MAT1A ENST00000871627.1

HGVSc / HGVSpc.*1021C>T

Exon rankExon 9 of 9

3_prime_UTR

Prot: ENSP00000541686.1UniProt: A0ACI8QDF3

MAT1A ENST00000871624.1

HGVSc / HGVSpc.*1021C>T

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 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.00000661	AC:1	Hom:0	AN:151310	Cov:32
GnomAD4 exome Warning	AF: 0.00	AC:0	Hom:0	AN:124	Cov:0
GnomAD4 genome Warning	AF: 0.00000661	AC:1	Hom:0	AN:151310	Cov:32
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:0	AN:13470	Cov:

Showing 4 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	3.2
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.6
DANN	Benign	0.67
GPN-Star LLR	N/A	0.038
GPN-Star score	N/A	-0.038
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