16-49592944-T-G

Position:

• chr16-49592944-T-G

Variant summary

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

The NM_001379286.1(ZNF423):​c.3601+33226A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,120 control chromosomes in the GnomAD database, including 19,025 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 0.48 (19025 hom., cov: 33)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF423	NM_001379286.1	c.3601+33226A>C		intron_variant		ENST00000563137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF423	ENST00000563137.7	c.3601+33226A>C		intron_variant		5	NM_001379286.1	P1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73542 AN: 152002 Hom.: 18982 Cov.: 33

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.484 AC: 73639 AN: 152120 Hom.: 19025 Cov.: 33 AF XY: 0.483 AC XY: 35928 AN XY: 74372

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.493

Alfa AF: 0.370 Hom.: 1353

Bravo AF: 0.493

Asia WGS AF: 0.612 AC: 2128 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	1.6
DANN	Benign	0.39

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: rs1345431; hg19: chr16-49626855;