rs2080353

Variant names:

• chr16-49624613-T-G
• rs2080353
• NM_001379286.1:c.3601+1557A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379286.1(ZNF423):​c.3601+1557A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,998 control chromosomes in the GnomAD database, including 9,891 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 0.35 (9891 hom., cov: 32)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF423	NM_001379286.1	c.3601+1557A>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.3601+1557A>C		intron_variant	Intron 5 of 7	5	NM_001379286.1	ENSP00000455588.3

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53233 AN: 151880 Hom.: 9871 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.351 AC: 53309 AN: 151998 Hom.: 9891 Cov.: 32 AF XY: 0.348 AC XY: 25813 AN XY: 74274

African (AFR) AF: 0.459 AC: 19027 AN: 41452

American (AMR) AF: 0.335 AC: 5122 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 972 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1145 AN: 5184

South Asian (SAS) AF: 0.288 AC: 1387 AN: 4808

European-Finnish (FIN) AF: 0.340 AC: 3584 AN: 10556

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.307 AC: 20843 AN: 67942

Other (OTH) AF: 0.320 AC: 675 AN: 2112

Alfa AF: 0.319 Hom.: 14543

Bravo AF: 0.357

Asia WGS AF: 0.285 AC: 995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.72
PhyloP100		-0.26
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: rs2080353; hg19: chr16-49658524;