rs587777776

Variant names:

• chr9-78328996-CCGGG-AGACCT
• rs587777776
• NM_058179.4:c.1023_1027delCCGGGinsAGACCT

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

The NM_058179.4(PSAT1):​c.1023_1027delCCGGGinsAGACCT​(p.Arg342AspfsTer6) variant causes a frameshift, missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSAT1 NM_058179.4 frameshift, missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 7.64
• Publications: 2 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
• PSAT deficiency

  Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• Neu-Laxova syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics
• Neu-Laxova syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0809 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-78328996-CCGGG-AGACCT is Pathogenic according to our data. Variant chr9-78328996-CCGGG-AGACCT is described in ClinVar as Pathogenic. ClinVar VariationId is 156362.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSAT1	NM_058179.4	c.1023_1027delCCGGGinsAGACCT	p.Arg342AspfsTer6	frameshift_variant, missense_variant	Exon 9 of 9	ENST00000376588.4	NP_478059.1
PSAT1	NM_021154.5	c.885_889delCCGGGinsAGACCT	p.Arg296AspfsTer6	frameshift_variant, missense_variant	Exon 8 of 8		NP_066977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSAT1	ENST00000376588.4	c.1023_1027delCCGGGinsAGACCT	p.Arg342AspfsTer6	frameshift_variant, missense_variant	Exon 9 of 9	1	NM_058179.4	ENSP00000365773.3
PSAT1	ENST00000347159.6	c.885_889delCCGGGinsAGACCT	p.Arg296AspfsTer6	frameshift_variant, missense_variant	Exon 8 of 8	1		ENSP00000317606.2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Neu-Laxova syndrome 2 Pathogenic:1

Sep 04, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided Other:1

-

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.6
Mutation Taster		=0/200	disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587777776; hg19: chr9-80943912;