Variant chr16-49731037-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001379286.1(ZNF423):c.101-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,551,884 control chromosomes in the GnomAD database, including 105,593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11717 hom., cov: 32)

Exomes 𝑓: 0.36 ( 93876 hom. )

Consequence

ZNF423
NM_001379286.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.15

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 16-49731037-C-T is Benign according to our data. Variant chr16-49731037-C-T is described in ClinVar as [Benign]. Clinvar id is 1239696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 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.101-66G>A		intron_variant		ENST00000563137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF423	ENST00000563137.7 linkuse as main transcript	c.101-66G>A		intron_variant		5	NM_001379286.1	P1

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58601

AN:

151914

Hom.:

11702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.486

Gnomad AMI

AF:

0.400

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.362

GnomAD4 exome

AF:

0.362

AC:

506790

AN:

1399852

Hom.:

93876

AF XY:

0.359

AC XY:

250181

AN XY:

696176

show subpopulations

Gnomad4 AFR exome

AF:

0.487

Gnomad4 AMR exome

AF:

0.236

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.216

Gnomad4 SAS exome

AF:

0.284

Gnomad4 FIN exome

AF:

0.363

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.386

AC:

58647

AN:

152032

Hom.:

11717

Cov.:

AF XY:

0.383

AC XY:

28480

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.486

Gnomad4 AMR

AF:

0.311

Gnomad4 ASJ

AF:

0.351

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.290

Gnomad4 FIN

AF:

0.355

Gnomad4 NFE

AF:

0.366

Gnomad4 OTH

AF:

0.360

Alfa

AF:

0.365

Hom.:

21338

Bravo

AF:

0.388

Asia WGS

AF:

0.253

AC:

884

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	clinical testing	GeneDx	May 17, 2021	- -
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

-0.79

CADD

Benign

8.9

DANN

Benign

0.77

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