chr9-78297247-GGTCCCGCCAAGCTGCCGCACTCAGTAA-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_058179.4(PSAT1):c.43_60+9del variant causes a splice donor, splice donor region, coding sequence, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,601,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
PSAT1
NM_058179.4 splice_donor, splice_donor_region, coding_sequence, intron
NM_058179.4 splice_donor, splice_donor_region, coding_sequence, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.03
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 6.1, offset of 29, new splice context is: cggGTgggt. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 9-78297247-GGTCCCGCCAAGCTGCCGCACTCAGTAA-G is Pathogenic according to our data. Variant chr9-78297247-GGTCCCGCCAAGCTGCCGCACTCAGTAA-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2140707.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PSAT1 | NM_058179.4 | c.43_60+9del | splice_donor_variant, splice_donor_region_variant, coding_sequence_variant, intron_variant | 1/9 | ENST00000376588.4 | NP_478059.1 | ||
| PSAT1 | NM_021154.5 | c.43_60+9del | splice_donor_variant, splice_donor_region_variant, coding_sequence_variant, intron_variant | 1/8 | NP_066977.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PSAT1 | ENST00000376588.4 | c.43_60+9del | splice_donor_variant, splice_donor_region_variant, coding_sequence_variant, intron_variant | 1/9 | 1 | NM_058179.4 | ENSP00000365773 | P1 | ||
| PSAT1 | ENST00000347159.6 | c.43_60+9del | splice_donor_variant, splice_donor_region_variant, coding_sequence_variant, intron_variant | 1/8 | 1 | ENSP00000317606 |
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 152208Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00000437 AC: 1AN: 228960Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 125686
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GnomAD4 exome AF: 0.00000345 AC: 5AN: 1449600Hom.: 0 AF XY: 0.00000277 AC XY: 2AN XY: 721234
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GnomAD4 genome 0.0000197 AC: 3AN: 152208Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74368
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neu-Laxova syndrome 2 Pathogenic:1
| Likely pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 12, 2023 | This variant results in the deletion of part of exon 1 (c.43_60+9del) of the PSAT1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PSAT1 are known to be pathogenic (PMID: 17436247, 25152457). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with PSAT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2140707). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at