Variant rs16947741 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001379286.1(ZNF423):c.1869G>A(p.Pro623=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 1,614,166 control chromosomes in the GnomAD database, including 890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 86 hom., cov: 33)

Exomes 𝑓: 0.029 ( 804 hom. )

Consequence

ZNF423
NM_001379286.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.72

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-49637307-C-T is Benign according to our data. Variant chr16-49637307-C-T is described in ClinVar as [Benign]. Clinvar id is 260523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-49637307-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.72 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF423	NM_001379286.1 linkuse as main transcript	c.1869G>A	p.Pro623=	synonymous_variant	4/8	ENST00000563137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF423	ENST00000563137.7 linkuse as main transcript	c.1869G>A	p.Pro623=	synonymous_variant	4/8	5	NM_001379286.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0290

AC:

4409

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0188

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.0611

Gnomad EAS

AF:

0.0121

Gnomad SAS

AF:

0.0450

Gnomad FIN

AF:

0.0386

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0326

Gnomad OTH

AF:

0.0393

GnomAD3 exomes

AF:

0.0311

AC:

7815

AN:

251348

Hom.:

162

AF XY:

0.0332

AC XY:

4516

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0197

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.0567

Gnomad EAS exome

AF:

0.0105

Gnomad SAS exome

AF:

0.0526

Gnomad FIN exome

AF:

0.0355

Gnomad NFE exome

AF:

0.0320

Gnomad OTH exome

AF:

0.0393

GnomAD4 exome

AF:

0.0294

AC:

43041

AN:

1461858

Hom.:

804

Cov.:

AF XY:

0.0308

AC XY:

22375

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0214

Gnomad4 AMR exome

AF:

0.0140

Gnomad4 ASJ exome

AF:

0.0577

Gnomad4 EAS exome

AF:

0.00605

Gnomad4 SAS exome

AF:

0.0521

Gnomad4 FIN exome

AF:

0.0341

Gnomad4 NFE exome

AF:

0.0281

Gnomad4 OTH exome

AF:

0.0316

GnomAD4 genome

AF:

0.0289

AC:

4409

AN:

152308

Hom.:

Cov.:

AF XY:

0.0301

AC XY:

2241

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0188

Gnomad4 AMR

AF:

0.0185

Gnomad4 ASJ

AF:

0.0611

Gnomad4 EAS

AF:

0.0120

Gnomad4 SAS

AF:

0.0450

Gnomad4 FIN

AF:

0.0386

Gnomad4 NFE

AF:

0.0326

Gnomad4 OTH

AF:

0.0394

Alfa

AF:

0.0310

Hom.:

Bravo

AF:

0.0255

Asia WGS

AF:

0.0420

AC:

144

AN:

3478

EpiCase

AF:

0.0326

EpiControl

AF:

0.0343

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephronophthisis 14

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.88

DANN

Benign

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over