16-49632652-T-C

Variant names:

• chr16-49632652-T-C
• rs1420676
• NM_001379286.1:c.3516+3008A>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.3516+3008A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,998 control chromosomes in the GnomAD database, including 28,137 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 (28137 hom., cov: 31)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.45
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 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.3516+3008A>G		intron	N/A	NP_001366215.1	A0A7P0Q1F0
	ZNF423	NM_015069.5		c.3492+3008A>G		intron	N/A	NP_055884.2
	ZNF423	NM_001271620.2		c.3312+3008A>G		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.3516+3008A>G		intron	N/A	ENSP00000455588.3	A0A7P0Q1F0
	ZNF423	ENST00000562520.1	TSL:1	c.3312+3008A>G		intron	N/A	ENSP00000457664.1	Q2M1K9-2
	ZNF423	ENST00000567169.5	TSL:1	c.3141+3008A>G		intron	N/A	ENSP00000455061.1	F5H7S1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87626 AN: 151878 Hom.: 28064 Cov.: 31

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.577 AC: 87768 AN: 151998 Hom.: 28137 Cov.: 31 AF XY: 0.574 AC XY: 42612 AN XY: 74290

African (AFR) AF: 0.883 AC: 36665 AN: 41516

American (AMR) AF: 0.485 AC: 7409 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1375 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2349 AN: 5120

South Asian (SAS) AF: 0.567 AC: 2724 AN: 4808

European-Finnish (FIN) AF: 0.448 AC: 4729 AN: 10562

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30880 AN: 67926

Other (OTH) AF: 0.516 AC: 1089 AN: 2112

Alfa AF: 0.490 Hom.: 72366

Bravo AF: 0.593

Asia WGS AF: 0.527 AC: 1835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0010
DANN	Benign	0.38
PhyloP100		-6.4
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: rs1420676; hg19: chr16-49666563;