rs117266679

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The ENST00000567169.5(ZNF423):c.-64C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00241 in 1,604,076 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 21 hom. )

Consequence

ZNF423
ENST00000567169.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.55

Publications

6 publications found

Variant links:

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 14
Inheritance: AD, Unknown, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
Joubert syndrome with oculorenal defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nephronophthisis 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nephronophthisis
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ZNF423 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 16-49638864-G-A is Benign according to our data. Variant chr16-49638864-G-A is described in ClinVar as Benign. ClinVar VariationId is 260531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00204 (310/152294) while in subpopulation EAS AF = 0.0182 (94/5176). AF 95% confidence interval is 0.0152. There are 1 homozygotes in GnomAd4. There are 154 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 21 AD,Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF423	NM_001379286.1 link	c.312C>T	p.Asp104Asp	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 link	c.312C>T	p.Asp104Asp	synonymous_variant	Exon 4 of 8	5	NM_001379286.1	ENSP00000455588.3

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

310

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.0181

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00393

AC:

957

AN:

243306

AF XY:

0.00423

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00196

Gnomad EAS exome

AF:

0.0239

Gnomad FIN exome

AF:

0.0000949

Gnomad NFE exome

AF:

0.00229

Gnomad OTH exome

AF:

0.00354

GnomAD4 exome

AF:

0.00245

AC:

3559

AN:

1451782

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

1879

AN XY:

720536

show subpopulations

African (AFR)

AF:

0.000420

AC:

AN:

33302

American (AMR)

AF:

0.00131

AC:

AN:

44196

Ashkenazi Jewish (ASJ)

AF:

0.00220

AC:

AN:

25448

East Asian (EAS)

AF:

0.0149

AC:

589

AN:

39556

South Asian (SAS)

AF:

0.00591

AC:

501

AN:

84788

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

53038

Middle Eastern (MID)

AF:

0.00594

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00193

AC:

2132

AN:

1105776

Other (OTH)

AF:

0.00267

AC:

160

AN:

59954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

223

446

668

891

1114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00204

AC:

310

AN:

152294

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

154

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41570

American (AMR)

AF:

0.00131

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3468

East Asian (EAS)

AF:

0.0182

AC:

AN:

5176

South Asian (SAS)

AF:

0.00415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00215

AC:

146

AN:

68022

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00253

Hom.:

Bravo

AF:

0.00224

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephronophthisis 14

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

ZNF423-related disorder

Benign:1

Jun 20, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

4.5

Mutation Taster

=228/72

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over