rs587777192
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_001312673.2(PCYT1A):c.847C>T(p.Arg283*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000992 in 1,612,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001312673.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152102Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251266Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135830
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1460894Hom.: 0 Cov.: 29 AF XY: 0.00000688 AC XY: 5AN XY: 726842
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152102Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74300
ClinVar
Submissions by phenotype
Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome Pathogenic:3
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not provided Uncertain:1
This sequence change creates a premature translational stop signal (p.Arg283*) in the PCYT1A gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in PCYT1A cause disease. This variant is present in population databases (rs587777192, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with retinal dystrophy and/or spondylometaphyseal dysplasia with cone-rod dystrophy (PMID: 24387990, 28272537). ClinVar contains an entry for this variant (Variation ID: 101060). 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