rs587777747

Variant names:

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

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 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 (★). 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

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]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-78300646-TG-T is Pathogenic according to our data. Variant chr9-78300646-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 1081.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSAT1	NM_058179.4	c.107delG	p.Gly36AlafsTer7	frameshift_variant	Exon 2 of 9	ENST00000376588.4	NP_478059.1
PSAT1	NM_021154.5	c.107delG	p.Gly36AlafsTer7	frameshift_variant	Exon 2 of 8		NP_066977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSAT1	ENST00000376588.4	c.107delG	p.Gly36AlafsTer7	frameshift_variant	Exon 2 of 9	1	NM_058179.4	ENSP00000365773.3
PSAT1	ENST00000347159.6	c.107delG	p.Gly36AlafsTer7	frameshift_variant	Exon 2 of 8	1		ENSP00000317606.2

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

GnomAD3 exomes AF: 0.0000121 AC: 3 AN: 248002 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 133976

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000531

Gnomad4 OTH exome AF: 0.0000166

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

Gnomad4 AFR AF: 0.0000484

Gnomad4 AMR AF: 0.000263

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neu-Laxova syndrome 2 Pathogenic:1

Nov 07, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change creates a premature translational stop signal (p.Gly36Alafs*7) in the PSAT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PSAT1 are known to be pathogenic (PMID: 17436247, 25152457). This variant is present in population databases (rs774147367, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with phosphoserine aminotransferase deficiency (PMID: 17436247). This variant is also known as c.delG107. ClinVar contains an entry for this variant (Variation ID: 1081). For these reasons, this variant has been classified as Pathogenic. -

PSAT deficiency Pathogenic:1

May 01, 2007

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided Other:1

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Dudley Research Group, Pacific Northwest Research Institute

Significance: not provided

Review Status: no classification provided

Collection Method: in vivo;research

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs587777747; hg19: chr9-80915562;