16-49618868-T-G

Position:

• chr16-49618868-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+7302A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,932 control chromosomes in the GnomAD database, including 5,941 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 0.28 (5941 hom., cov: 32)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF423	NM_001379286.1	c.3601+7302A>C		intron_variant		ENST00000563137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF423	ENST00000563137.7	c.3601+7302A>C		intron_variant		5	NM_001379286.1	P1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41772 AN: 151814 Hom.: 5930 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.275 AC: 41833 AN: 151932 Hom.: 5941 Cov.: 32 AF XY: 0.278 AC XY: 20677 AN XY: 74262

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.253

Alfa AF: 0.238 Hom.: 7140

Bravo AF: 0.274

Asia WGS AF: 0.350 AC: 1221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.81

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: rs16944158; hg19: chr16-49652779;