chr12-89425203-A-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_172240.3(POC1B):āc.1290T>Gā(p.Asp430Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,212 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 (ā ).
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.1290T>G | p.Asp430Glu | missense_variant | 11/12 | ENST00000313546.8 | |
POC1B | NM_001199777.2 | c.1164T>G | p.Asp388Glu | missense_variant | 10/11 | ||
POC1B | NR_037659.2 | n.1293T>G | non_coding_transcript_exon_variant | 11/12 | |||
POC1B | NR_037660.2 | n.1329T>G | non_coding_transcript_exon_variant | 9/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POC1B | ENST00000313546.8 | c.1290T>G | p.Asp430Glu | missense_variant | 11/12 | 1 | NM_172240.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251414Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135880
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461856Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727234
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74512
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 17, 2022 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1511198). This variant has not been reported in the literature in individuals affected with POC1B-related conditions. This variant is present in population databases (rs539980702, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 430 of the POC1B protein (p.Asp430Glu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at