chr16-49638609-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.567T>C(p.Arg189Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,613,480 control chromosomes in the GnomAD database, including 174,513 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 25640 hom., cov: 32)

Exomes 𝑓: 0.45 ( 148873 hom. )

Consequence

ZNF423
NM_001379286.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.615

Publications

21 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=-0.56).

BP6

Variant 16-49638609-A-G is Benign according to our data. Variant chr16-49638609-A-G is described in ClinVar as Benign. ClinVar VariationId is 260538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.615 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF423	NM_001379286.1 link	c.567T>C	p.Arg189Arg	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.567T>C	p.Arg189Arg	synonymous_variant	Exon 4 of 8	5	NM_001379286.1	ENSP00000455588.3		A0A7P0Q1F0

Frequencies

GnomAD3 genomes

AF:

0.550

AC:

83556

AN:

151906

Hom.:

25580

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.459

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.431

Gnomad OTH

AF:

0.478

GnomAD2 exomes

AF:

0.472

AC:

118238

AN:

250524

AF XY:

0.466

show subpopulations

Gnomad AFR exome

AF:

0.857

Gnomad AMR exome

AF:

0.479

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.457

Gnomad FIN exome

AF:

0.450

Gnomad NFE exome

AF:

0.422

Gnomad OTH exome

AF:

0.430

GnomAD4 exome

AF:

0.445

AC:

650415

AN:

1461456

Hom.:

148873

Cov.:

AF XY:

0.445

AC XY:

323878

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.858

AC:

28723

AN:

33480

American (AMR)

AF:

0.474

AC:

21188

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

9595

AN:

26134

East Asian (EAS)

AF:

0.469

AC:

18598

AN:

39692

South Asian (SAS)

AF:

0.514

AC:

44326

AN:

86248

European-Finnish (FIN)

AF:

0.447

AC:

23771

AN:

53158

Middle Eastern (MID)

AF:

0.419

AC:

2414

AN:

5768

European-Non Finnish (NFE)

AF:

0.427

AC:

475042

AN:

1111908

Other (OTH)

AF:

0.443

AC:

26758

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

26137

52274

78410

104547

130684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14660

29320

43980

58640

73300

<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:

0.550

AC:

83685

AN:

152024

Hom.:

25640

Cov.:

AF XY:

0.546

AC XY:

40601

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.846

AC:

35112

AN:

41484

American (AMR)

AF:

0.458

AC:

7004

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1297

AN:

3468

East Asian (EAS)

AF:

0.459

AC:

2366

AN:

5158

South Asian (SAS)

AF:

0.506

AC:

2427

AN:

4798

European-Finnish (FIN)

AF:

0.442

AC:

4671

AN:

10568

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.431

AC:

29260

AN:

67944

Other (OTH)

AF:

0.480

AC:

1014

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1653

3306

4960

6613

8266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.482

Hom.:

18526

Bravo

AF:

0.565

Asia WGS

AF:

0.483

AC:

1680

AN:

3478

EpiCase

AF:

0.423

EpiControl

AF:

0.423

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephronophthisis 14

Benign:2

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

- -

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

-0.56

CADD

Benign

0.78

(source)

DANN

Benign

0.61

PhyloP100

-0.61

Mutation Taster

=100/0

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