10-80274919-A-G

Variant names:

• chr10-80274919-A-G
• rs10788545
• NM_000429.3:c.951+98T>C

Variant summary

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

The ENST00000372213.8(MAT1A):​c.951+98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,415,934 control chromosomes in the GnomAD database, including 360,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (46445 hom., cov: 32)
  • Exomes 𝑓: 0.70 (313643 hom.)
• Consequence: MAT1A ENST00000372213.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.24
• Publications: 6 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=-0.99).
• BP6: Variant 10-80274919-A-G is Benign according to our data. Variant chr10-80274919-A-G is described in ClinVar as Benign. ClinVar VariationId is 1228160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000372213.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	NM_000429.3	MANE Select	c.951+98T>C		intron	N/A	NP_000420.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	ENST00000372213.8	TSL:1 MANE Select	c.951+98T>C		intron	N/A	ENSP00000361287.3
	MAT1A	ENST00000480845.1	TSL:3	n.183+98T>C		intron	N/A
	MAT1A	ENST00000485270.5	TSL:2	n.463+98T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117163 AN: 152014 Hom.: 46386 Cov.: 32

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.764

GnomAD4 exome AF: 0.700 AC: 884129 AN: 1263802 Hom.: 313643 AF XY: 0.702 AC XY: 441859 AN XY: 629310

African (AFR) AF: 0.944 AC: 27278 AN: 28886

American (AMR) AF: 0.808 AC: 28629 AN: 35414

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 18129 AN: 24084

East Asian (EAS) AF: 0.944 AC: 33094 AN: 35046

South Asian (SAS) AF: 0.836 AC: 63344 AN: 75808

European-Finnish (FIN) AF: 0.697 AC: 30421 AN: 43648

Middle Eastern (MID) AF: 0.811 AC: 3099 AN: 3820

European-Non Finnish (NFE) AF: 0.665 AC: 640743 AN: 963602

Other (OTH) AF: 0.736 AC: 39392 AN: 53494

GnomAD4 genome AF: 0.771 AC: 117282 AN: 152132 Hom.: 46445 Cov.: 32 AF XY: 0.776 AC XY: 57665 AN XY: 74352

African (AFR) AF: 0.937 AC: 38904 AN: 41538

American (AMR) AF: 0.783 AC: 11969 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2595 AN: 3470

East Asian (EAS) AF: 0.968 AC: 5003 AN: 5170

South Asian (SAS) AF: 0.851 AC: 4104 AN: 4820

European-Finnish (FIN) AF: 0.696 AC: 7341 AN: 10548

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44958 AN: 67972

Other (OTH) AF: 0.767 AC: 1621 AN: 2114

Alfa AF: 0.722 Hom.: 5032

Bravo AF: 0.784

Asia WGS AF: 0.890 AC: 3094 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.030
DANN	Benign	0.34
PhyloP100		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs10788545; hg19: chr10-82034675;