16-49635885-G-A

Variant names:

• chr16-49635885-G-A
• rs150027129
• NM_001379286.1:c.3291C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001379286.1(ZNF423):​c.3291C>T​(p.Tyr1097Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00518 in 1,583,464 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (26 hom.)
• Consequence: ZNF423 NM_001379286.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.39
• Publications: 2 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-49635885-G-A is Benign according to our data. Variant chr16-49635885-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 197822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 26 AD,Unknown,AR gene

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.3291C>T	p.Tyr1097Tyr	synonymous	Exon 4 of 8	NP_001366215.1
	ZNF423	NM_015069.5		c.3267C>T	p.Tyr1089Tyr	synonymous	Exon 4 of 8	NP_055884.2
	ZNF423	NM_001271620.2		c.3087C>T	p.Tyr1029Tyr	synonymous	Exon 4 of 8	NP_001258549.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF423	ENST00000563137.7	TSL:5 MANE Select	c.3291C>T	p.Tyr1097Tyr	synonymous	Exon 4 of 8	ENSP00000455588.3
	ZNF423	ENST00000562520.1	TSL:1	c.3087C>T	p.Tyr1029Tyr	synonymous	Exon 4 of 8	ENSP00000457664.1
	ZNF423	ENST00000567169.5	TSL:1	c.2916C>T	p.Tyr972Tyr	synonymous	Exon 2 of 6	ENSP00000455061.1

Frequencies

GnomAD3 genomes AF: 0.00394 AC: 599 AN: 152222 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00235

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00650

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00632

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00413 AC: 896 AN: 217032 AF XY: 0.00416

Gnomad AFR exome AF: 0.00153

Gnomad AMR exome AF: 0.00196

Gnomad ASJ exome AF: 0.00235

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00485

Gnomad NFE exome AF: 0.00636

Gnomad OTH exome AF: 0.00399

GnomAD4 exome AF: 0.00531 AC: 7600 AN: 1431124 Hom.: 26 Cov.: 31 AF XY: 0.00529 AC XY: 3754 AN XY: 709132

African (AFR) AF: 0.00101 AC: 33 AN: 32674

American (AMR) AF: 0.00181 AC: 74 AN: 40794

Ashkenazi Jewish (ASJ) AF: 0.00244 AC: 58 AN: 23784

East Asian (EAS) AF: 0.00 AC: 0 AN: 39454

South Asian (SAS) AF: 0.00195 AC: 157 AN: 80322

European-Finnish (FIN) AF: 0.00486 AC: 248 AN: 51030

Middle Eastern (MID) AF: 0.00554 AC: 31 AN: 5592

European-Non Finnish (NFE) AF: 0.00615 AC: 6753 AN: 1098414

Other (OTH) AF: 0.00417 AC: 246 AN: 59060

GnomAD4 genome AF: 0.00393 AC: 598 AN: 152340 Hom.: 1 Cov.: 33 AF XY: 0.00388 AC XY: 289 AN XY: 74496

African (AFR) AF: 0.000673 AC: 28 AN: 41586

American (AMR) AF: 0.00235 AC: 36 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.00650 AC: 69 AN: 10620

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00632 AC: 430 AN: 68026

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00454 Hom.: 2

Bravo AF: 0.00340

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 27, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 17, 2019

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Aug 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZNF423: BP4, BP7, BS2

Nephronophthisis 14 Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.15
DANN	Benign	0.59
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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: rs150027129; hg19: chr16-49669796;