NM_000429.3:c.92-9C>G

Variant names:

• chr10-80285598-G-C
• rs10887721
• NM_000429.3:c.92-9C>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000429.3(MAT1A):​c.92-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,587,578 control chromosomes in the GnomAD database, including 22,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (5159 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17032 hom.)
• Consequence: MAT1A NM_000429.3 intron
• Scores: Splicing: ADA: 0.4505
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.300
• Publications: 9 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, ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 10-80285598-G-C is Benign according to our data. Variant chr10-80285598-G-C is described in ClinVar as Benign. ClinVar VariationId is 256108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	NM_000429.3	MANE Select	c.92-9C>G		intron	N/A	NP_000420.1	Q00266

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	ENST00000372213.8	TSL:1 MANE Select	c.92-9C>G		intron	N/A	ENSP00000361287.3	Q00266
	MAT1A	ENST00000871627.1		c.92-9C>G		intron	N/A	ENSP00000541686.1
	MAT1A	ENST00000871624.1		c.92-9C>G		intron	N/A	ENSP00000541683.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32849 AN: 151980 Hom.: 5144 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.138 AC: 34758 AN: 251282 AF XY: 0.136

Gnomad AFR exome AF: 0.456

Gnomad AMR exome AF: 0.0758

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.000870

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.142 AC: 203208 AN: 1435480 Hom.: 17032 Cov.: 27 AF XY: 0.140 AC XY: 100100 AN XY: 715876

African (AFR) AF: 0.461 AC: 15238 AN: 33038

American (AMR) AF: 0.0827 AC: 3697 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 4648 AN: 25958

East Asian (EAS) AF: 0.000531 AC: 21 AN: 39574

South Asian (SAS) AF: 0.103 AC: 8850 AN: 85684

European-Finnish (FIN) AF: 0.115 AC: 6148 AN: 53410

Middle Eastern (MID) AF: 0.170 AC: 974 AN: 5716

European-Non Finnish (NFE) AF: 0.142 AC: 154902 AN: 1087960

Other (OTH) AF: 0.147 AC: 8730 AN: 59456

GnomAD4 genome AF: 0.216 AC: 32893 AN: 152098 Hom.: 5159 Cov.: 32 AF XY: 0.212 AC XY: 15745 AN XY: 74356

African (AFR) AF: 0.446 AC: 18487 AN: 41464

American (AMR) AF: 0.129 AC: 1968 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 590 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0914 AC: 440 AN: 4816

European-Finnish (FIN) AF: 0.111 AC: 1174 AN: 10584

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9632 AN: 67980

Other (OTH) AF: 0.180 AC: 381 AN: 2112

Alfa AF: 0.171 Hom.: 850

Bravo AF: 0.229

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hepatic methionine adenosyltransferase deficiency (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.56
PhyloP100		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.45
dbscSNV1_RF	Benign	0.37
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: rs10887721; hg19: chr10-82045354;