16-49523530-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001379286.1(ZNF423):c.3849+94T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,034,490 control chromosomes in the GnomAD database, including 162,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (29724 hom., cov: 33)
  • Exomes 𝑓: 0.54 (132372 hom.)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.906

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-49523530-A-C is Benign according to our data. Variant chr16-49523530-A-C is described in ClinVar as [Benign]. Clinvar id is 1292296.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF423	NM_001379286.1	c.3849+94T>G		intron_variant		ENST00000563137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF423	ENST00000563137.7	c.3849+94T>G		intron_variant		5	NM_001379286.1	P1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93285 AN: 151932 Hom.: 29672 Cov.: 33

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.617

GnomAD4 exome AF: 0.544 AC: 480154 AN: 882440 Hom.: 132372 AF XY: 0.540 AC XY: 244428 AN XY: 452614

Gnomad4 AFR exome AF: 0.790

Gnomad4 AMR exome AF: 0.485

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.489

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.544

Gnomad4 OTH exome AF: 0.562

GnomAD4 genome AF: 0.614 AC: 93401 AN: 152050 Hom.: 29724 Cov.: 33 AF XY: 0.610 AC XY: 45345 AN XY: 74304

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.622

Alfa AF: 0.584 Hom.: 3318

Bravo AF: 0.623

Asia WGS AF: 0.544 AC: 1892 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	-0.90
Cadd	Benign	0.32
Dann	Benign	0.66

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: rs2287313; hg19: chr16-49557441; COSMIC: COSV52181801; COSMIC: COSV52181801;