16-49716879-T-C

Variant names:

• chr16-49716879-T-C
• rs17281813
• NM_001379286.1:c.301+13892A>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.301+13892A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,152 control chromosomes in the GnomAD database, including 6,113 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 0.26 (6113 hom., cov: 32)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• 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=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 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.301+13892A>G		intron	N/A	NP_001366215.1	A0A7P0Q1F0
	ZNF423	NM_015069.5		c.277+13892A>G		intron	N/A	NP_055884.2
	ZNF423	NM_001271620.2		c.97+13892A>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.301+13892A>G		intron	N/A	ENSP00000455588.3	A0A7P0Q1F0
	ZNF423	ENST00000562520.1	TSL:1	c.97+13892A>G		intron	N/A	ENSP00000457664.1	Q2M1K9-2
	ZNF423	ENST00000561648.5	TSL:5	c.277+13892A>G		intron	N/A	ENSP00000455426.1	Q2M1K9-1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39072 AN: 152034 Hom.: 6116 Cov.: 32

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.257 AC: 39080 AN: 152152 Hom.: 6113 Cov.: 32 AF XY: 0.259 AC XY: 19250 AN XY: 74378

African (AFR) AF: 0.0739 AC: 3070 AN: 41522

American (AMR) AF: 0.293 AC: 4472 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 979 AN: 3472

East Asian (EAS) AF: 0.194 AC: 1000 AN: 5166

South Asian (SAS) AF: 0.294 AC: 1416 AN: 4822

European-Finnish (FIN) AF: 0.376 AC: 3977 AN: 10588

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23260 AN: 67986

Other (OTH) AF: 0.274 AC: 577 AN: 2106

Alfa AF: 0.301 Hom.: 20300

Bravo AF: 0.242

Asia WGS AF: 0.234 AC: 812 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	0.71
PhyloP100		-0.14
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: rs17281813; hg19: chr16-49750790;