rs149371639

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001379286.1(ZNF423):c.1560C>T(p.Asp520Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

ZNF423
NM_001379286.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.44

Publications

0 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-49637616-G-A is Benign according to our data. Variant chr16-49637616-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 473056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.44 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379286.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZNF423	NM_001379286.1	MANE Select	c.1560C>T	p.Asp520Asp	synonymous	Exon 4 of 8	NP_001366215.1
ZNF423	NM_015069.5		c.1536C>T	p.Asp512Asp	synonymous	Exon 4 of 8	NP_055884.2
ZNF423	NM_001271620.2		c.1356C>T	p.Asp452Asp	synonymous	Exon 4 of 8	NP_001258549.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZNF423	ENST00000563137.7	TSL:5 MANE Select	c.1560C>T	p.Asp520Asp	synonymous	Exon 4 of 8	ENSP00000455588.3
ZNF423	ENST00000562520.1	TSL:1	c.1356C>T	p.Asp452Asp	synonymous	Exon 4 of 8	ENSP00000457664.1
ZNF423	ENST00000567169.5	TSL:1	c.1185C>T	p.Asp395Asp	synonymous	Exon 2 of 6	ENSP00000455061.1

Frequencies

GnomAD3 genomes

AF:

0.000677

AC:

103

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000195

AC:

AN:

251118

AF XY:

0.000184

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000883

AC:

129

AN:

1461734

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.00221

AC:

AN:

33478

American (AMR)

AF:

0.000134

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53264

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000315

AC:

AN:

1112010

Other (OTH)

AF:

0.000132

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000676

AC:

103

AN:

152328

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00238

AC:

AN:

41570

American (AMR)

AF:

0.0000654

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000308

Hom.:

Bravo

AF:

0.000827

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ZNF423: BP4, BP7

Nephronophthisis 14

Benign:1

Nov 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ZNF423-related disorder

Benign:1

Jul 26, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.045

(source)

DANN

Benign

0.55

PhyloP100

-1.4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over