16-49636479-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001379286.1(ZNF423):c.2697T>C(p.Cys899Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,613,386 control chromosomes in the GnomAD database, including 37,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3466 hom., cov: 33)

Exomes 𝑓: 0.21 ( 34115 hom. )

Consequence

ZNF423
NM_001379286.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0430

Publications

12 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 16-49636479-A-G is Benign according to our data. Variant chr16-49636479-A-G is described in ClinVar as Benign. ClinVar VariationId is 260529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.043 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF423	NM_001379286.1 link	c.2697T>C	p.Cys899Cys	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.2697T>C	p.Cys899Cys	synonymous_variant	Exon 4 of 8	5	NM_001379286.1	ENSP00000455588.3

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31868

AN:

151988

Hom.:

3451

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.191

GnomAD2 exomes

AF:

0.223

AC:

56054

AN:

251180

AF XY:

0.217

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.356

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.204

GnomAD4 exome

AF:

0.212

AC:

310268

AN:

1461280

Hom.:

34115

Cov.:

AF XY:

0.210

AC XY:

152503

AN XY:

726930

show subpopulations

African (AFR)

AF:

0.204

AC:

6816

AN:

33480

American (AMR)

AF:

0.343

AC:

15345

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

4057

AN:

26136

East Asian (EAS)

AF:

0.219

AC:

8700

AN:

39700

South Asian (SAS)

AF:

0.165

AC:

14249

AN:

86258

European-Finnish (FIN)

AF:

0.256

AC:

13503

AN:

52830

Middle Eastern (MID)

AF:

0.124

AC:

714

AN:

5768

European-Non Finnish (NFE)

AF:

0.211

AC:

234707

AN:

1111998

Other (OTH)

AF:

0.202

AC:

12177

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

18111

36223

54334

72446

90557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8140

16280

24420

32560

40700

<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:

0.210

AC:

31927

AN:

152106

Hom.:

3466

Cov.:

AF XY:

0.209

AC XY:

15516

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.203

AC:

8418

AN:

41486

American (AMR)

AF:

0.251

AC:

3844

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

536

AN:

3466

East Asian (EAS)

AF:

0.203

AC:

1052

AN:

5170

South Asian (SAS)

AF:

0.168

AC:

807

AN:

4808

European-Finnish (FIN)

AF:

0.243

AC:

2579

AN:

10594

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14102

AN:

67974

Other (OTH)

AF:

0.190

AC:

401

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1364

2729

4093

5458

6822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.211

Hom.:

6572

Bravo

AF:

0.216

Asia WGS

AF:

0.180

AC:

627

AN:

3478

EpiCase

AF:

0.202

EpiControl

AF:

0.201

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.93

(source)

DANN

Benign

0.62

PhyloP100

-0.043

Mutation Taster

=96/4

polymorphism (auto)

(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

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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