rs2242466

chr16-49846803-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379286.1(ZNF423):c.40+8932A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,114 control chromosomes in the GnomAD database, including 6,274 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6274 hom., cov: 32)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF423	NM_001379286.1	c.40+8932A>G		intron_variant		ENST00000563137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF423	ENST00000563137.7	c.40+8932A>G		intron_variant		5	NM_001379286.1	P1
ZNF423	ENST00000562520.1	c.-165+10938A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43275 AN: 151996 Hom.: 6266 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.291

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.285 AC: 43319 AN: 152114 Hom.: 6274 Cov.: 32 AF XY: 0.282 AC XY: 20982 AN XY: 74378

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.289

Alfa AF: 0.266 Hom.: 6932

Bravo AF: 0.289

Asia WGS AF: 0.210 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.083
Dann	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2242466; hg19: chr16-49880714;