rs2242466

Variant names:

• chr16-49846803-T-C
• rs2242466
• NM_001379286.1:c.40+8932A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• nephronophthisis 14

  Inheritance: AD, Unknown, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• Joubert syndrome with oculorenal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000300023 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379286.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF423	NM_001379286.1	MANE Select	c.40+8932A>G		intron	N/A	NP_001366215.1
	ZNF423	NM_001271620.2		c.-165+10938A>G		intron	N/A	NP_001258549.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF423	ENST00000563137.7	TSL:5 MANE Select	c.40+8932A>G		intron	N/A	ENSP00000455588.3
	ZNF423	ENST00000562520.1	TSL:1	c.-165+10938A>G		intron	N/A	ENSP00000457664.1
	ENSG00000300023	ENST00000768224.1		n.498+875A>G		intron	N/A

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

African (AFR) AF: 0.355 AC: 14711 AN: 41486

American (AMR) AF: 0.281 AC: 4303 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3470

East Asian (EAS) AF: 0.229 AC: 1181 AN: 5164

South Asian (SAS) AF: 0.207 AC: 997 AN: 4818

European-Finnish (FIN) AF: 0.234 AC: 2479 AN: 10594

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17652 AN: 67978

Other (OTH) AF: 0.289 AC: 609 AN: 2108

Alfa AF: 0.269 Hom.: 9073

Bravo AF: 0.289

Asia WGS AF: 0.210 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.083
DANN	Benign	0.47
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2242466; hg19: chr16-49880714;