16-49716879-T-C

Position:

• chr16-49716879-T-C

Variant summary

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

The NM_001379286.1(ZNF423):​c.301+13892A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,152 control chromosomes in the GnomAD database, including 6,113 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 0.26 (6113 hom., cov: 32)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

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=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF423	NM_001379286.1	c.301+13892A>G		intron_variant		ENST00000563137.7	NP_001366215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF423	ENST00000563137.7	c.301+13892A>G		intron_variant		5	NM_001379286.1	ENSP00000455588.3
ZNF423	ENST00000562520.1	c.97+13892A>G		intron_variant		1		ENSP00000457664.1
ZNF423	ENST00000561648.5	c.277+13892A>G		intron_variant		5		ENSP00000455426.1
ZNF423	ENST00000562871.5	c.97+13892A>G		intron_variant		5		ENSP00000457928.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39072 AN: 152034 Hom.: 6116 Cov.: 32

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.257 AC: 39080 AN: 152152 Hom.: 6113 Cov.: 32 AF XY: 0.259 AC XY: 19250 AN XY: 74378

Gnomad4 AFR AF: 0.0739

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.274

Alfa AF: 0.319 Hom.: 15002

Bravo AF: 0.242

Asia WGS AF: 0.234 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.71

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: rs17281813; hg19: chr16-49750790;