rs587777747

Variant names:

• chr9-78300646-TG-T
• rs587777747
• NM_058179.4:c.107delG

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PP5_Moderate

The NM_058179.4(PSAT1):​c.107delG​(p.Gly36AlafsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,608,416 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G36G) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: PSAT1 NM_058179.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2 O:1
• Conservation: PhyloP100: 8.42
• Publications: 7 publications found

Genes affected

PSAT1 (HGNC:19129): (phosphoserine aminotransferase 1) This gene encodes a member of the class-V pyridoxal-phosphate-dependent aminotransferase family. The encoded protein is a phosphoserine aminotransferase and decreased expression may be associated with schizophrenia. Mutations in this gene are also associated with phosphoserine aminotransferase deficiency. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 1, 3, and 8. [provided by RefSeq, Jul 2013]

PSAT1 Gene-Disease associations (from GenCC):

• neurometabolic disorder due to serine deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Neu-Laxova syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics
• PSAT deficiency

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• Neu-Laxova syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 9-78300646-TG-T is Pathogenic according to our data. Variant chr9-78300646-TG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 1081.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058179.4. 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
	PSAT1	NM_058179.4	MANE Select	c.107delG	p.Gly36AlafsTer7	frameshift	Exon 2 of 9	NP_478059.1	Q9Y617-1
	PSAT1	NM_021154.5		c.107delG	p.Gly36AlafsTer7	frameshift	Exon 2 of 8	NP_066977.1	Q9Y617-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSAT1	ENST00000376588.4	TSL:1 MANE Select	c.107delG	p.Gly36AlafsTer7	frameshift	Exon 2 of 9	ENSP00000365773.3	Q9Y617-1
	PSAT1	ENST00000347159.6	TSL:1	c.107delG	p.Gly36AlafsTer7	frameshift	Exon 2 of 8	ENSP00000317606.2	Q9Y617-2
	PSAT1	ENST00000906296.1		c.107delG	p.Gly36AlafsTer7	frameshift	Exon 2 of 9	ENSP00000576355.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151730 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248002 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000419 AC: 61 AN: 1456686 Hom.: 0 Cov.: 32 AF XY: 0.0000428 AC XY: 31 AN XY: 724316

African (AFR) AF: 0.00 AC: 0 AN: 33236

American (AMR) AF: 0.0000227 AC: 1 AN: 44150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25992

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 85058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4750

European-Non Finnish (NFE) AF: 0.0000531 AC: 59 AN: 1110540

Other (OTH) AF: 0.0000166 AC: 1 AN: 60118

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151730 Hom.: 0 Cov.: 31 AF XY: 0.0000540 AC XY: 4 AN XY: 74066

African (AFR) AF: 0.0000484 AC: 2 AN: 41302

American (AMR) AF: 0.000263 AC: 4 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Neu-Laxova syndrome 2 (1)
1	-	-	PSAT deficiency (1)
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.4
Mutation Taster		=0/200	disease causing (ClinVar)

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: rs587777747; hg19: chr9-80915562;