12-89525132-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_172240.3(POC1B):c.88G>A(p.Gly30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G30D) has been classified as Uncertain significance.
Frequency
Consequence
NM_172240.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POC1B | ENST00000313546.8 | c.88G>A | p.Gly30Ser | missense_variant | Exon 2 of 12 | 1 | NM_172240.3 | ENSP00000323302.3 | ||
POC1B-GALNT4 | ENST00000548729.5 | c.88G>A | p.Gly30Ser | missense_variant | Exon 2 of 3 | 2 | ENSP00000447852.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251310Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135870
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461690Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727158
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Cone-rod dystrophy 20 Uncertain:1
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not provided Uncertain:1
This sequence change replaces glycine with serine at codon 30 of the POC1B protein (p.Gly30Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with POC1B-related conditions. 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 POC1B protein function. 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