rs2292155

Positions:

• chr16-49731037-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.15

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 -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	c.101-66G>A		intron_variant		ENST00000563137.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58601 AN: 151914 Hom.: 11702 Cov.: 32

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

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.: 32 AF XY: 0.383 AC XY: 28480 AN XY: 74282

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

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

Other links and lift over

dbSNP: rs2292155; hg19: chr16-49764948; COSMIC: COSV52190317;