15-84783054-C-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_014630.3(ZNF592):c.379C>A(p.Leu127Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000606 in 1,614,196 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00063 ( 10 hom. )
Consequence
ZNF592
NM_014630.3 missense
NM_014630.3 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: -0.0610
Genes affected
ZNF592 (HGNC:28986): (zinc finger protein 592) This gene is thought to play a role in a complex developmental pathway and the regulation of genes involved in cerebellar development. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia. [provided by RefSeq, Jan 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0033040345).
BP6
Variant 15-84783054-C-A is Benign according to our data. Variant chr15-84783054-C-A is described in ClinVar as [Benign]. Clinvar id is 3043504.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAdExome4 at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF592 | NM_014630.3 | c.379C>A | p.Leu127Met | missense_variant | 4/11 | ENST00000560079.7 | |
ZNF592 | XM_005254996.4 | c.379C>A | p.Leu127Met | missense_variant | 3/10 | ||
ZNF592 | XM_011522246.3 | c.379C>A | p.Leu127Met | missense_variant | 4/11 | ||
ZNF592 | XM_011522247.3 | c.379C>A | p.Leu127Met | missense_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF592 | ENST00000560079.7 | c.379C>A | p.Leu127Met | missense_variant | 4/11 | 1 | NM_014630.3 | P1 | |
ZNF592 | ENST00000559607.1 | c.379C>A | p.Leu127Met | missense_variant, NMD_transcript_variant | 2/9 | 1 | |||
ZNF592 | ENST00000299927.4 | c.379C>A | p.Leu127Met | missense_variant | 1/8 | 2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000394 AC: 60AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00114 AC: 287AN: 251264Hom.: 1 AF XY: 0.00161 AC XY: 219AN XY: 135848
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GnomAD4 exome AF: 0.000629 AC: 919AN: 1461892Hom.: 10 Cov.: 32 AF XY: 0.000920 AC XY: 669AN XY: 727248
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GnomAD4 genome AF: 0.000394 AC: 60AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.000645 AC XY: 48AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
ZNF592-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 27, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Loss of methylation at K126 (P = 0.0396);Loss of methylation at K126 (P = 0.0396);
MVP
MPC
0.91
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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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