chr2-27378156-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_144631.6(ZNF513):c.1015T>C(p.Cys339Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,613,476 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. C339C) has been classified as Uncertain significance.
Frequency
Consequence
NM_144631.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF513 | NM_144631.6 | c.1015T>C | p.Cys339Arg | missense_variant | 4/4 | ENST00000323703.11 | |
ZNF513 | NM_001201459.2 | c.829T>C | p.Cys277Arg | missense_variant | 3/3 | ||
ZNF513 | XM_005264143.4 | c.511T>C | p.Cys171Arg | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF513 | ENST00000323703.11 | c.1015T>C | p.Cys339Arg | missense_variant | 4/4 | 1 | NM_144631.6 | P4 | |
ZNF513 | ENST00000407879.1 | c.829T>C | p.Cys277Arg | missense_variant | 3/3 | 1 | A1 | ||
ZNF513 | ENST00000491924.1 | n.260-126T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152106Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000184 AC: 46AN: 250314Hom.: 3 AF XY: 0.000258 AC XY: 35AN XY: 135416
GnomAD4 exome AF: 0.000109 AC: 160AN: 1461252Hom.: 3 Cov.: 32 AF XY: 0.000142 AC XY: 103AN XY: 726960
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74416
ClinVar
Submissions by phenotype
Retinitis pigmentosa 58 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 10, 2010 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 07, 2023 | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 339 of the ZNF513 protein (p.Cys339Arg). This variant is present in population databases (rs267607182, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with autosmal recessive retinitis pigmentosa (PMID: 20797688). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 28). 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. Experimental studies have shown that this missense change affects ZNF513 function (PMID: 20797688). 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. - |
Retinitis Pigmentosa, Dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Oct 20, 2017 | The ZNF513 c.1015T>C (p.Cys339Arg) variant has been reported in a homozygous state in four siblings from a consanguineous family with retinitis pigmentosa (Li et al. 2010). The unaffected parents and three unaffected siblings were heterozygous for this variant. This variant was absent from 242 control chromosomes, but is reported at a frequency of 0.001637 in the South Asian population from the Exome Aggregation Consortium. In zebrafish, the p.Cys339Arg variant showed reduced rescue of retinal phenotype compared to wildtype (31% vs. 86%). The evidence for this variant is limited, therefore the p.Cys339Arg variant is classified as a variant of unknown significance but is suspicious for pathogenicity for autosomal recessive retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at