rs2080501

chr16-49609655-G-Achr16-49609655-G-C

Variant summary

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

The NM_001379286.1(ZNF423):c.3601+16515C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,838 control chromosomes in the GnomAD database, including 27,536 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 0.58 (27536 hom., cov: 31)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF423	NM_001379286.1	c.3601+16515C>T		intron_variant		ENST00000563137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF423	ENST00000563137.7	c.3601+16515C>T		intron_variant		5	NM_001379286.1	P1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87354 AN: 151718 Hom.: 27469 Cov.: 31

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.576 AC: 87496 AN: 151838 Hom.: 27536 Cov.: 31 AF XY: 0.574 AC XY: 42571 AN XY: 74210

Gnomad4 AFR AF: 0.856

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.501

Alfa AF: 0.472 Hom.: 34812

Bravo AF: 0.584

Asia WGS AF: 0.543 AC: 1890 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	3.3
Dann	Benign	0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs2080501; hg19: chr16-49643566;