dbSNP rs113531514: ZNF423:p.Pro1117Pro (chr16-49635825-C-T) – ACMG Classification: Benign (-21 pts)

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.3351G>A(p.Pro1117Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 1,607,256 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 68 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 79 hom. )

Consequence

ZNF423
NM_001379286.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.17

Publications

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

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=-0.52).

BP6

Variant 16-49635825-C-T is Benign according to our data. Variant chr16-49635825-C-T is described in ClinVar as Benign. ClinVar VariationId is 260534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

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	UniProt
ZNF423	NM_001379286.1	MANE Select	c.3351G>A	p.Pro1117Pro	synonymous	Exon 4 of 8	NP_001366215.1	A0A7P0Q1F0
ZNF423	NM_015069.5		c.3327G>A	p.Pro1109Pro	synonymous	Exon 4 of 8	NP_055884.2
ZNF423	NM_001271620.2		c.3147G>A	p.Pro1049Pro	synonymous	Exon 4 of 8	NP_001258549.1	Q2M1K9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF423	ENST00000563137.7	TSL:5 MANE Select	c.3351G>A	p.Pro1117Pro	synonymous	Exon 4 of 8	ENSP00000455588.3	A0A7P0Q1F0
ZNF423	ENST00000562520.1	TSL:1	c.3147G>A	p.Pro1049Pro	synonymous	Exon 4 of 8	ENSP00000457664.1	Q2M1K9-2
ZNF423	ENST00000567169.5	TSL:1	c.2976G>A	p.Pro992Pro	synonymous	Exon 2 of 6	ENSP00000455061.1	F5H7S1

Frequencies

GnomAD3 genomes

AF:

0.0174

AC:

2650

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0590

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00896

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.00456

AC:

1086

AN:

237914

AF XY:

0.00335

show subpopulations

Gnomad AFR exome

AF:

0.0594

Gnomad AMR exome

AF:

0.00297

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000323

Gnomad OTH exome

AF:

0.00223

GnomAD4 exome

AF:

0.00200

AC:

2907

AN:

1455010

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1253

AN XY:

723558

show subpopulations

African (AFR)

AF:

0.0601

AC:

1999

AN:

33242

American (AMR)

AF:

0.00378

AC:

165

AN:

43660

Ashkenazi Jewish (ASJ)

AF:

0.00392

AC:

101

AN:

25778

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39632

South Asian (SAS)

AF:

0.000128

AC:

AN:

85660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51772

Middle Eastern (MID)

AF:

0.00349

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.000279

AC:

309

AN:

1109432

Other (OTH)

AF:

0.00501

AC:

301

AN:

60100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

177

354

530

707

884

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.0176

AC:

2672

AN:

152246

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1276

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0593

AC:

2464

AN:

41536

American (AMR)

AF:

0.00895

AC:

137

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

68010

Other (OTH)

AF:

0.0132

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

114

228

342

456

570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00215

Hom.:

Bravo

AF:

0.0197

Asia WGS

AF:

0.00347

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nephronophthisis 14 (2)

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.5

(source)

DANN

Benign

0.75

PhyloP100

-1.2

Mutation Taster

=100/0

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

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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

Computational scores

Splicing

Publications

Other links and lift over