rs1344528

Positions:

• chr16-49508017-G-T

Variant summary

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

The NM_001379286.1(ZNF423):​c.3849+15607C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 151,964 control chromosomes in the GnomAD database, including 30,660 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 0.62 (30660 hom., cov: 31)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF423	NM_001379286.1	c.3849+15607C>A		intron_variant		ENST00000563137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF423	ENST00000563137.7	c.3849+15607C>A		intron_variant		5	NM_001379286.1	P1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94312 AN: 151846 Hom.: 30609 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.621 AC: 94420 AN: 151964 Hom.: 30660 Cov.: 31 AF XY: 0.617 AC XY: 45822 AN XY: 74236

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.620

Alfa AF: 0.547 Hom.: 25425

Bravo AF: 0.634

Asia WGS AF: 0.558 AC: 1943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.21
DANN	Benign	0.31

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: rs1344528; hg19: chr16-49541928;