rs117592972
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_001379286.1(ZNF423):c.3180G>A(p.Ala1060=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000715 in 1,602,080 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 Benign (★★).
Frequency
Genomes: 𝑓 0.00058 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00073 ( 1 hom. )
Consequence
ZNF423
NM_001379286.1 synonymous
NM_001379286.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.88
Genes affected
ZNF423 (HGNC:16762): (zinc finger protein 423) The protein encoded by this gene is a nuclear protein that belongs to the family of Kruppel-like C2H2 zinc finger proteins. It functions as a DNA-binding transcription factor by using distinct zinc fingers in different signaling pathways. Thus, it is thought that this gene may have multiple roles in signal transduction during development. Mutations in this gene are associated with nephronophthisis-14 and Joubert syndrome-19. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 16-49635996-C-T is Benign according to our data. Variant chr16-49635996-C-T is described in ClinVar as [Benign]. Clinvar id is 473061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-49635996-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-3.88 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000584 (89/152302) while in subpopulation EAS AF= 0.012 (62/5174). AF 95% confidence interval is 0.00959. There are 0 homozygotes in gnomad4. There are 42 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF423 | NM_001379286.1 | c.3180G>A | p.Ala1060= | synonymous_variant | 4/8 | ENST00000563137.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF423 | ENST00000563137.7 | c.3180G>A | p.Ala1060= | synonymous_variant | 4/8 | 5 | NM_001379286.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000572 AC: 87AN: 152184Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00114 AC: 276AN: 242938Hom.: 0 AF XY: 0.00101 AC XY: 132AN XY: 131250
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GnomAD4 exome AF: 0.000729 AC: 1057AN: 1449778Hom.: 1 Cov.: 31 AF XY: 0.000676 AC XY: 486AN XY: 719248
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GnomAD4 genome ? AF: 0.000584 AC: 89AN: 152302Hom.: 0 Cov.: 33 AF XY: 0.000564 AC XY: 42AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Nephronophthisis 14 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
ZNF423-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 20, 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
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Name
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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