12-89425208-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_172240.3(POC1B):c.1285A>G(p.Thr429Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,614,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POC1B | NM_172240.3 | c.1285A>G | p.Thr429Ala | missense_variant | 11/12 | ENST00000313546.8 | |
POC1B | NM_001199777.2 | c.1159A>G | p.Thr387Ala | missense_variant | 10/11 | ||
POC1B | NR_037659.2 | n.1288A>G | non_coding_transcript_exon_variant | 11/12 | |||
POC1B | NR_037660.2 | n.1324A>G | non_coding_transcript_exon_variant | 9/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POC1B | ENST00000313546.8 | c.1285A>G | p.Thr429Ala | missense_variant | 11/12 | 1 | NM_172240.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000795 AC: 20AN: 251416Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135874
GnomAD4 exome AF: 0.0000575 AC: 84AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45AN XY: 727234
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152324Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74494
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 429 of the POC1B protein (p.Thr429Ala). This variant is present in population databases (rs553428980, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with POC1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1051551). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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