16-49796293-A-G

Variant names:

• chr16-49796293-A-G
• rs8060157
• NM_001379286.1:c.41-6747T>C

Variant summary

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

The NM_001379286.1(ZNF423):​c.41-6747T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,748 control chromosomes in the GnomAD database, including 25,102 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 0.57 (25102 hom., cov: 30)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650
• Publications: 13 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 = 0.62 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.41-6747T>C		intron	N/A	NP_001366215.1	A0A7P0Q1F0
	ZNF423	NM_015069.5		c.17-6747T>C		intron	N/A	NP_055884.2
	ZNF423	NM_001271620.2		c.-164-6747T>C		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.41-6747T>C		intron	N/A	ENSP00000455588.3	A0A7P0Q1F0
	ZNF423	ENST00000562520.1	TSL:1	c.-164-6747T>C		intron	N/A	ENSP00000457664.1	Q2M1K9-2
	ZNF423	ENST00000561648.5	TSL:5	c.17-6747T>C		intron	N/A	ENSP00000455426.1	Q2M1K9-1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87025 AN: 151630 Hom.: 25063 Cov.: 30

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.574 AC: 87119 AN: 151748 Hom.: 25102 Cov.: 30 AF XY: 0.576 AC XY: 42692 AN XY: 74152

African (AFR) AF: 0.627 AC: 25930 AN: 41388

American (AMR) AF: 0.517 AC: 7880 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2140 AN: 3472

East Asian (EAS) AF: 0.544 AC: 2774 AN: 5098

South Asian (SAS) AF: 0.594 AC: 2852 AN: 4800

European-Finnish (FIN) AF: 0.545 AC: 5747 AN: 10552

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37911 AN: 67890

Other (OTH) AF: 0.561 AC: 1180 AN: 2104

Alfa AF: 0.562 Hom.: 52986

Bravo AF: 0.572

Asia WGS AF: 0.557 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.37
DANN	Benign	0.44
PhyloP100		-0.65
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: rs8060157; hg19: chr16-49830204;