chr16-49609655-G-A

Variant names:

• chr16-49609655-G-A
• rs2080501
• NM_001379286.1:c.3601+16515C>T

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+16515C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,838 control chromosomes in the GnomAD database, including 27,536 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 0.58 (27536 hom., cov: 31)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780
• Publications: 8 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: Unknown, AD, AR Classification: STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• ciliopathy

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Joubert syndrome with oculorenal defect

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF423	NM_001379286.1	MANE Select	c.3601+16515C>T		intron	N/A	NP_001366215.1	A0A7P0Q1F0
	ZNF423	NM_015069.5		c.3577+16515C>T		intron	N/A	NP_055884.2
	ZNF423	NM_001271620.2		c.3397+16515C>T		intron	N/A	NP_001258549.1	Q2M1K9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF423	ENST00000563137.7	TSL:5 MANE Select	c.3601+16515C>T		intron	N/A	ENSP00000455588.3	A0A7P0Q1F0
	ZNF423	ENST00000562520.1	TSL:1	c.3397+16515C>T		intron	N/A	ENSP00000457664.1	Q2M1K9-2
	ZNF423	ENST00000567169.5	TSL:1	c.3226+16515C>T		intron	N/A	ENSP00000455061.1	F5H7S1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87354 AN: 151718 Hom.: 27469 Cov.: 31

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.576 AC: 87496 AN: 151838 Hom.: 27536 Cov.: 31 AF XY: 0.574 AC XY: 42571 AN XY: 74210

African (AFR) AF: 0.856 AC: 35487 AN: 41464

American (AMR) AF: 0.470 AC: 7166 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1524 AN: 3466

East Asian (EAS) AF: 0.475 AC: 2451 AN: 5162

South Asian (SAS) AF: 0.567 AC: 2723 AN: 4806

European-Finnish (FIN) AF: 0.480 AC: 5039 AN: 10494

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31573 AN: 67890

Other (OTH) AF: 0.501 AC: 1057 AN: 2110

Alfa AF: 0.492 Hom.: 81951

Bravo AF: 0.584

Asia WGS AF: 0.543 AC: 1890 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.3
DANN	Benign	0.24
PhyloP100		0.078
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: rs2080501; hg19: chr16-49643566;