chr16-49581676-T-C

Variant names:

• chr16-49581676-T-C
• rs4785326
• NM_001379286.1:c.3601+44494A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379286.1(ZNF423):​c.3601+44494A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,078 control chromosomes in the GnomAD database, including 9,707 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 0.36 (9707 hom., cov: 32)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398
• Publications: 6 publications found

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]

ZNF423 Gene-Disease associations (from GenCC):

• nephronophthisis 14

  Inheritance: AD, Unknown, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• Joubert syndrome with oculorenal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379286.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF423	NM_001379286.1	MANE Select	c.3601+44494A>G		intron	N/A	NP_001366215.1
	ZNF423	NM_015069.5		c.3577+44494A>G		intron	N/A	NP_055884.2
	ZNF423	NM_001271620.2		c.3397+44494A>G		intron	N/A	NP_001258549.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF423	ENST00000563137.7	TSL:5 MANE Select	c.3601+44494A>G		intron	N/A	ENSP00000455588.3
	ZNF423	ENST00000562520.1	TSL:1	c.3397+44494A>G		intron	N/A	ENSP00000457664.1
	ZNF423	ENST00000567169.5	TSL:1	c.3226+44494A>G		intron	N/A	ENSP00000455061.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54107 AN: 151960 Hom.: 9686 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.356 AC: 54182 AN: 152078 Hom.: 9707 Cov.: 32 AF XY: 0.354 AC XY: 26315 AN XY: 74358

African (AFR) AF: 0.353 AC: 14625 AN: 41488

American (AMR) AF: 0.327 AC: 4995 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1425 AN: 3470

East Asian (EAS) AF: 0.434 AC: 2243 AN: 5164

South Asian (SAS) AF: 0.324 AC: 1559 AN: 4808

European-Finnish (FIN) AF: 0.367 AC: 3887 AN: 10578

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24293 AN: 67966

Other (OTH) AF: 0.351 AC: 742 AN: 2112

Alfa AF: 0.359 Hom.: 19626

Bravo AF: 0.355

Asia WGS AF: 0.370 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.55
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4785326; hg19: chr16-49615587;