rs11595587

Variant names:

• chr10-80289576-G-A
• rs11595587
• NM_000429.3:c.-153C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-80289576-G-A
• chr10-80289576-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000429.3(MAT1A):​c.-153C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 694,976 control chromosomes in the GnomAD database, including 340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (77 hom., cov: 32)
  • Exomes 𝑓: 0.028 (263 hom.)
• Consequence: MAT1A NM_000429.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.127
• 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=-0.7).
• BP6: Variant 10-80289576-G-A is Benign according to our data. Variant chr10-80289576-G-A is described in ClinVar as Benign. ClinVar VariationId is 301205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0247 (3757/152120) while in subpopulation NFE AF = 0.0365 (2485/68000). AF 95% confidence interval is 0.0353. There are 77 homozygotes in GnomAd4. There are 1828 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 77 AD,AR gene

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.-153C>T		5_prime_UTR	Exon 1 of 9	NP_000420.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	ENST00000372213.8	TSL:1 MANE Select	c.-153C>T		5_prime_UTR	Exon 1 of 9	ENSP00000361287.3
	MAT1A	ENST00000871627.1		c.-153C>T		5_prime_UTR	Exon 1 of 9	ENSP00000541686.1
	MAT1A	ENST00000871624.1		c.-153C>T		5_prime_UTR	Exon 1 of 9	ENSP00000541683.1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3754 AN: 152002 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.00611

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.0426

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0278 AC: 15075 AN: 542856 Hom.: 263 Cov.: 5 AF XY: 0.0266 AC XY: 7811 AN XY: 294154

African (AFR) AF: 0.00810 AC: 125 AN: 15426

American (AMR) AF: 0.0219 AC: 747 AN: 34118

Ashkenazi Jewish (ASJ) AF: 0.0212 AC: 412 AN: 19460

East Asian (EAS) AF: 0.00 AC: 0 AN: 31608

South Asian (SAS) AF: 0.00648 AC: 400 AN: 61694

European-Finnish (FIN) AF: 0.0384 AC: 1342 AN: 34976

Middle Eastern (MID) AF: 0.0221 AC: 62 AN: 2802

European-Non Finnish (NFE) AF: 0.0358 AC: 11214 AN: 313014

Other (OTH) AF: 0.0260 AC: 773 AN: 29758

GnomAD4 genome AF: 0.0247 AC: 3757 AN: 152120 Hom.: 77 Cov.: 32 AF XY: 0.0246 AC XY: 1828 AN XY: 74374

African (AFR) AF: 0.00610 AC: 253 AN: 41498

American (AMR) AF: 0.0248 AC: 379 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4824

European-Finnish (FIN) AF: 0.0426 AC: 450 AN: 10566

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0365 AC: 2485 AN: 68000

Other (OTH) AF: 0.0242 AC: 51 AN: 2108

Alfa AF: 0.0326 Hom.: 366

Bravo AF: 0.0231

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.1
DANN	Benign	0.85
PhyloP100		-0.13
PromoterAI		0.025	Neutral
Mutation Taster		=300/0	polymorphism

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: rs11595587; hg19: chr10-82049332;