Variant 16-49491327-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001379286.1(ZNF423):c.3850-23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,613,774 control chromosomes in the GnomAD database, including 4,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 453 hom., cov: 32)

Exomes 𝑓: 0.020 ( 3839 hom. )

Consequence

ZNF423
NM_001379286.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.41

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 16-49491327-C-T is Benign according to our data. Variant chr16-49491327-C-T is described in ClinVar as [Benign]. Clinvar id is 1231602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 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.3850-23G>A		intron_variant		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.3850-23G>A		intron_variant		5	NM_001379286.1	ENSP00000455588	P1

Frequencies

GnomAD3 genomes

AF:

0.0308

AC:

4690

AN:

152114

Hom.:

451

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.0617

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00315

Gnomad OTH

AF:

0.0325

GnomAD3 exomes

AF:

0.0626

AC:

15733

AN:

251152

Hom.:

2029

AF XY:

0.0514

AC XY:

6979

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.00406

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.00486

Gnomad EAS exome

AF:

0.276

Gnomad SAS exome

AF:

0.00470

Gnomad FIN exome

AF:

0.0583

Gnomad NFE exome

AF:

0.00296

Gnomad OTH exome

AF:

0.0365

GnomAD4 exome

AF:

0.0204

AC:

29835

AN:

1461542

Hom.:

3839

Cov.:

AF XY:

0.0189

AC XY:

13721

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.00539

Gnomad4 EAS exome

AF:

0.330

Gnomad4 SAS exome

AF:

0.00559

Gnomad4 FIN exome

AF:

0.0582

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.0217

GnomAD4 genome

AF:

0.0308

AC:

4695

AN:

152232

Hom.:

453

Cov.:

AF XY:

0.0362

AC XY:

2691

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00431

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.281

Gnomad4 SAS

AF:

0.00808

Gnomad4 FIN

AF:

0.0617

Gnomad4 NFE

AF:

0.00315

Gnomad4 OTH

AF:

0.0322

Alfa

AF:

0.0146

Hom.:

Bravo

AF:

0.0391

Asia WGS

AF:

0.122

AC:

425

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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