16-49635783-G-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_001379286.1(ZNF423):c.3393C>G(p.Pro1131Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P1131P) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ZNF423
NM_001379286.1 synonymous
NM_001379286.1 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -3.89
Publications
1 publications found
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]
ZNF423 Gene-Disease associations (from GenCC):
- nephronophthisis 14Inheritance: AD, Unknown, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
- Joubert syndrome with oculorenal defectInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- nephronophthisis 2Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- nephronophthisisInheritance: AR Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP7
Synonymous conserved (PhyloP=-3.89 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ZNF423 | NM_001379286.1 | c.3393C>G | p.Pro1131Pro | 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.3393C>G | p.Pro1131Pro | synonymous_variant | Exon 4 of 8 | 5 | NM_001379286.1 | ENSP00000455588.3 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152206
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
AF:
Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000404 AC: 1AN: 247514 AF XY: 0.00000744 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
247514
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460334Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726506 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460334
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
726506
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33464
American (AMR)
AF:
AC:
0
AN:
44654
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26124
East Asian (EAS)
AF:
AC:
0
AN:
39670
South Asian (SAS)
AF:
AC:
0
AN:
86220
European-Finnish (FIN)
AF:
AC:
0
AN:
52298
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111768
Other (OTH)
AF:
AC:
0
AN:
60368
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74360 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
152206
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74360
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
41450
American (AMR)
AF:
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5188
South Asian (SAS)
AF:
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68036
Other (OTH)
AF:
AC:
0
AN:
2090
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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