NM_001379286.1:c.3602-35014T>C

Variant names:

• chr16-49560508-A-G
• rs11647781
• NM_001379286.1:c.3602-35014T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001379286.1(ZNF423):​c.3602-35014T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,028 control chromosomes in the GnomAD database, including 5,795 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 0.27 (5795 hom., cov: 32)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• Publications: 8 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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF423	NM_001379286.1	c.3602-35014T>C		intron_variant	Intron 5 of 7	ENST00000563137.7	NP_001366215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF423	ENST00000563137.7	c.3602-35014T>C		intron_variant	Intron 5 of 7	5	NM_001379286.1	ENSP00000455588.3

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40909 AN: 151910 Hom.: 5784 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.269 AC: 40959 AN: 152028 Hom.: 5795 Cov.: 32 AF XY: 0.271 AC XY: 20174 AN XY: 74306

African (AFR) AF: 0.175 AC: 7250 AN: 41476

American (AMR) AF: 0.266 AC: 4073 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1202 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2193 AN: 5154

South Asian (SAS) AF: 0.286 AC: 1375 AN: 4810

European-Finnish (FIN) AF: 0.339 AC: 3575 AN: 10538

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.300 AC: 20385 AN: 67978

Other (OTH) AF: 0.288 AC: 608 AN: 2112

Alfa AF: 0.289 Hom.: 12062

Bravo AF: 0.259

Asia WGS AF: 0.332 AC: 1159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Benign	0.67
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11647781; hg19: chr16-49594419;