chr8-96273388-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014754.3(PTDSS1):c.269A>G(p.Asn90Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000138 in 1,450,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. N90N) has been classified as Benign.
Frequency
Consequence
NM_014754.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTDSS1 | NM_014754.3 | c.269A>G | p.Asn90Ser | missense_variant, splice_region_variant | 2/13 | ENST00000517309.6 | |
LOC105375652 | XR_928431.3 | n.91-7051T>C | intron_variant, non_coding_transcript_variant | ||||
PTDSS1 | NM_001290225.2 | c.1A>G | p.Met1? | start_lost, splice_region_variant | 2/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTDSS1 | ENST00000517309.6 | c.269A>G | p.Asn90Ser | missense_variant, splice_region_variant | 2/13 | 1 | NM_014754.3 | P1 | |
PTDSS1 | ENST00000337004.8 | c.269A>G | p.Asn90Ser | missense_variant, splice_region_variant, NMD_transcript_variant | 2/11 | 1 | |||
PTDSS1 | ENST00000517557.5 | n.343A>G | splice_region_variant, non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000407 AC: 1AN: 245462Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132576
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1450554Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1AN XY: 722012
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 04, 2023 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 90 of the PTDSS1 protein (p.Asn90Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with PTDSS1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at