rs7500906

Variant names:

• chr16-49762920-G-A
• rs7500906
• NM_001379286.1:c.100+26567C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-49762920-G-A
• chr16-49762920-G-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.100+26567C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,090 control chromosomes in the GnomAD database, including 23,792 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 0.55 (23792 hom., cov: 33)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF423	NM_001379286.1	c.100+26567C>T		intron_variant	Intron 2 of 7	ENST00000563137.7	NP_001366215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF423	ENST00000563137.7	c.100+26567C>T		intron_variant	Intron 2 of 7	5	NM_001379286.1	ENSP00000455588.3

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83072 AN: 151972 Hom.: 23752 Cov.: 33

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.547 AC: 83160 AN: 152090 Hom.: 23792 Cov.: 33 AF XY: 0.548 AC XY: 40697 AN XY: 74326

African (AFR) AF: 0.727 AC: 30149 AN: 41496

American (AMR) AF: 0.548 AC: 8371 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1505 AN: 3470

East Asian (EAS) AF: 0.537 AC: 2773 AN: 5162

South Asian (SAS) AF: 0.485 AC: 2340 AN: 4826

European-Finnish (FIN) AF: 0.501 AC: 5283 AN: 10548

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 31014 AN: 67978

Other (OTH) AF: 0.528 AC: 1118 AN: 2116

Alfa AF: 0.397 Hom.: 1484

Bravo AF: 0.563

Asia WGS AF: 0.478 AC: 1665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
DANN	Benign	0.52
PhyloP100		-1.4
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: rs7500906; hg19: chr16-49796831;