2-27377416-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_144631.6(ZNF513):c.*129G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000775 in 1,026,952 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00047 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00083 ( 1 hom. )
Consequence
ZNF513
NM_144631.6 3_prime_UTR
NM_144631.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.922
Genes affected
SNX17 (HGNC:14979): (sorting nexin 17) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein does not contain a coiled coil region, like some family members, but contains a B41 domain. This protein interacts with the cytoplasmic domain of P-selectin, and may function in the intracellular trafficking of P-selectin. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2012]
ZNF513 (HGNC:26498): (zinc finger protein 513) The protein encoded by this gene is a possible transcriptional regulator involved in retinal development. Defects in this gene can be a cause of autosomal-recessive retinitis pigmentosa. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SNX17 | NM_014748.4 | c.*697C>T | 3_prime_UTR_variant | 15/15 | ENST00000233575.7 | ||
ZNF513 | NM_144631.6 | c.*129G>A | 3_prime_UTR_variant | 4/4 | ENST00000323703.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SNX17 | ENST00000233575.7 | c.*697C>T | 3_prime_UTR_variant | 15/15 | 1 | NM_014748.4 | P1 | ||
ZNF513 | ENST00000323703.11 | c.*129G>A | 3_prime_UTR_variant | 4/4 | 1 | NM_144631.6 | P4 | ||
ZNF513 | ENST00000407879.1 | c.*129G>A | 3_prime_UTR_variant | 3/3 | 1 | A1 | |||
SNX17 | ENST00000537606.5 | c.*697C>T | 3_prime_UTR_variant | 14/14 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000467 AC: 71AN: 152146Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000509 AC: 75AN: 147456Hom.: 1 AF XY: 0.000560 AC XY: 45AN XY: 80378
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GnomAD4 exome AF: 0.000829 AC: 725AN: 874688Hom.: 1 Cov.: 12 AF XY: 0.000813 AC XY: 367AN XY: 451576
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Retinitis Pigmentosa, Dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Retinitis pigmentosa Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at