16-49618868-T-G

Variant names:

• chr16-49618868-T-G
• rs16944158
• NM_001379286.1:c.3601+7302A>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.3601+7302A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,932 control chromosomes in the GnomAD database, including 5,941 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 0.28 (5941 hom., cov: 32)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 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+7302A>C		intron	N/A	NP_001366215.1
	ZNF423	NM_015069.5		c.3577+7302A>C		intron	N/A	NP_055884.2
	ZNF423	NM_001271620.2		c.3397+7302A>C		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+7302A>C		intron	N/A	ENSP00000455588.3
	ZNF423	ENST00000562520.1	TSL:1	c.3397+7302A>C		intron	N/A	ENSP00000457664.1
	ZNF423	ENST00000567169.5	TSL:1	c.3226+7302A>C		intron	N/A	ENSP00000455061.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41772 AN: 151814 Hom.: 5930 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.275 AC: 41833 AN: 151932 Hom.: 5941 Cov.: 32 AF XY: 0.278 AC XY: 20677 AN XY: 74262

African (AFR) AF: 0.340 AC: 14074 AN: 41388

American (AMR) AF: 0.223 AC: 3409 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1621 AN: 5146

South Asian (SAS) AF: 0.401 AC: 1924 AN: 4802

European-Finnish (FIN) AF: 0.266 AC: 2817 AN: 10576

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.242 AC: 16471 AN: 67958

Other (OTH) AF: 0.253 AC: 533 AN: 2108

Alfa AF: 0.249 Hom.: 12907

Bravo AF: 0.274

Asia WGS AF: 0.350 AC: 1221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.81
PhyloP100		-0.086
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: rs16944158; hg19: chr16-49652779;