9-78304891-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_058179.4(PSAT1):c.348G>C(p.Lys116Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_058179.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PSAT1 | NM_058179.4 | c.348G>C | p.Lys116Asn | missense_variant | Exon 4 of 9 | ENST00000376588.4 | NP_478059.1 | |
PSAT1 | NM_021154.5 | c.348G>C | p.Lys116Asn | missense_variant | Exon 4 of 8 | NP_066977.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251476Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135910
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461360Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 726998
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Neu-Laxova syndrome 2 Uncertain:1
This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 116 of the PSAT1 protein (p.Lys116Asn). This variant is present in population databases (rs41277897, gnomAD 0.003%). 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: 976987). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PSAT1 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect PSAT1 function (PMID: 32077105). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
not provided Other:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at