15-77028590-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003978.5(PSTPIP1):āc.454G>Cā(p.Asp152His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,603,452 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. D152D) has been classified as Likely benign.
Frequency
Consequence
NM_003978.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSTPIP1 | NM_003978.5 | c.454G>C | p.Asp152His | missense_variant | 7/15 | ENST00000558012.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSTPIP1 | ENST00000558012.6 | c.454G>C | p.Asp152His | missense_variant | 7/15 | 1 | NM_003978.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.89e-7 AC: 1AN: 1451218Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 720988
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 08, 2023 | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PSTPIP1 protein function. ClinVar contains an entry for this variant (Variation ID: 534750). This variant has not been reported in the literature in individuals affected with PSTPIP1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 152 of the PSTPIP1 protein (p.Asp152His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at