16-49491327-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.41

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]

ACMG classification

Verdict is Benign. Variant got -12 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_single_submitter, 1 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	UniProt
ZNF423	NM_001379286.1	c.3850-23G>A		intron_variant		ENST00000563137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF423	ENST00000563137.7	c.3850-23G>A		intron_variant		5	NM_001379286.1	P1

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4690 AN: 152114 Hom.: 451 Cov.: 32

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

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.: 31 AF XY: 0.0189 AC XY: 13721 AN XY: 727086

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.: 32 AF XY: 0.0362 AC XY: 2691 AN XY: 74430

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.: 26

Bravo AF: 0.0391

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
Cadd	Benign	20
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

Other links and lift over

dbSNP: rs12445683; hg19: chr16-49525238; COSMIC: COSV52177798;