chr2-27377546-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_144631.6(ZNF513):c.1625G>T(p.Ter542LeuextTer29) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
ZNF513
NM_144631.6 stop_lost
NM_144631.6 stop_lost
Scores
1
1
5
Clinical Significance
Conservation
PhyloP100: 1.99
Genes affected
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_144631.6 Downstream stopcodon found after 7 codons.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF513 | NM_144631.6 | c.1625G>T | p.Ter542LeuextTer29 | stop_lost | 4/4 | ENST00000323703.11 | |
SNX17 | NM_014748.4 | downstream_gene_variant | ENST00000233575.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF513 | ENST00000323703.11 | c.1625G>T | p.Ter542LeuextTer29 | stop_lost | 4/4 | 1 | NM_144631.6 | P4 | |
ZNF513 | ENST00000407879.1 | c.1439G>T | p.Ter480LeuextTer29 | stop_lost | 3/3 | 1 | A1 | ||
SNX17 | ENST00000233575.7 | downstream_gene_variant | 1 | NM_014748.4 | P1 | ||||
SNX17 | ENST00000537606.5 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152186Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461692Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727156
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 06, 2023 | This sequence change disrupts the translational stop signal of the ZNF513 mRNA. It is expected to extend the length of the ZNF513 protein by 29 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ZNF513-related conditions. ClinVar contains an entry for this variant (Variation ID: 1487848). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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
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Name
Calibrated prediction
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Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
MutationTaster
Benign
N;N
Vest4
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -33
Find out detailed SpliceAI scores and Pangolin per-transcript scores at