rs77996576
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001379286.1(ZNF423):c.2535C>T(p.Thr845Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,614,026 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 36 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 33 hom. )
Consequence
ZNF423
NM_001379286.1 synonymous
NM_001379286.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.996
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 16-49636641-G-A is Benign according to our data. Variant chr16-49636641-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.996 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1784/152256) while in subpopulation AFR AF= 0.0407 (1691/41544). AF 95% confidence interval is 0.0391. There are 36 homozygotes in gnomad4. There are 860 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 36 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZNF423 | NM_001379286.1 | c.2535C>T | p.Thr845Thr | synonymous_variant | Exon 4 of 8 | ENST00000563137.7 | NP_001366215.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNF423 | ENST00000563137.7 | c.2535C>T | p.Thr845Thr | synonymous_variant | Exon 4 of 8 | 5 | NM_001379286.1 | ENSP00000455588.3 |
Frequencies
GnomAD3 genomes AF: 0.0117 AC: 1787AN: 152138Hom.: 37 Cov.: 33
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GnomAD3 exomes AF: 0.00325 AC: 816AN: 250852Hom.: 16 AF XY: 0.00238 AC XY: 323AN XY: 135648
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GnomAD4 exome AF: 0.00125 AC: 1823AN: 1461770Hom.: 33 Cov.: 37 AF XY: 0.00109 AC XY: 794AN XY: 727166
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GnomAD4 genome AF: 0.0117 AC: 1784AN: 152256Hom.: 36 Cov.: 33 AF XY: 0.0116 AC XY: 860AN XY: 74444
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Nephronophthisis 14 Benign:3
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Dec 05, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Sep 27, 2021
Fulgent Genetics, Fulgent Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not specified Benign:1
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PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not provided Benign:1
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Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
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