Variant rs3803665 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.567T>C(p.Arg189=) 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

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=-0.56).

BP6

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

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/exons	MANE	Protein	UniProt
ZNF423	NM_001379286.1 linkuse as main transcript	c.567T>C	p.Arg189=	synonymous_variant	4/8	ENST00000563137.7	NP_001366215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF423	ENST00000563137.7 linkuse as main transcript	c.567T>C	p.Arg189=	synonymous_variant	4/8	5	NM_001379286.1	ENSP00000455588	P1

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

GnomAD3 exomes

AF:

0.472

AC:

118238

AN:

250524

Hom.:

29558

AF XY:

0.466

AC XY:

63154

AN XY:

135538

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 SAS exome

AF:

0.512

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

Gnomad4 AFR exome

AF:

0.858

Gnomad4 AMR exome

AF:

0.474

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.469

Gnomad4 SAS exome

AF:

0.514

Gnomad4 FIN exome

AF:

0.447

Gnomad4 NFE exome

AF:

0.427

Gnomad4 OTH exome

AF:

0.443

GnomAD4 genome

AF:

0.550

AC:

83685

AN:

152024

Hom.:

25640

Cov.:

AF XY:

0.546

AC XY:

40601

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.846

Gnomad4 AMR

AF:

0.458

Gnomad4 ASJ

AF:

0.374

Gnomad4 EAS

AF:

0.459

Gnomad4 SAS

AF:

0.506

Gnomad4 FIN

AF:

0.442

Gnomad4 NFE

AF:

0.431

Gnomad4 OTH

AF:

0.480

Alfa

AF:

0.476

Hom.:

13528

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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.78

DANN

Benign

0.61

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