rs150027129

chr16-49635885-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001379286.1(ZNF423):c.3291C>T(p.Tyr1097=) 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:6
• Conservation: PhyloP100: -1.39

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]

ACMG classification

Verdict is Benign. Variant got -21 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 [Likely_benign]. Clinvar id is 197822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-49635885-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00393 (598/152340) while in subpopulation NFE AF= 0.00632 (430/68026). AF 95% confidence interval is 0.00583. There are 1 homozygotes in gnomad4. There are 289 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF423	NM_001379286.1	c.3291C>T	p.Tyr1097=	synonymous_variant	4/8	ENST00000563137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF423	ENST00000563137.7	c.3291C>T	p.Tyr1097=	synonymous_variant	4/8	5	NM_001379286.1	P1

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

GnomAD3 exomes AF: 0.00413 AC: 896 AN: 217032 Hom.: 3 AF XY: 0.00416 AC XY: 487 AN XY: 117150

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 SAS exome AF: 0.00242

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

Gnomad4 AFR exome AF: 0.00101

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.00244

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00195

Gnomad4 FIN exome AF: 0.00486

Gnomad4 NFE exome AF: 0.00615

Gnomad4 OTH exome AF: 0.00417

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

Gnomad4 AFR AF: 0.000673

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00650

Gnomad4 NFE AF: 0.00632

Gnomad4 OTH AF: 0.00378

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:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 27, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jul 17, 2019	- -

Nephronophthisis 14 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

ZNF423: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.15
Dann	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs150027129; hg19: chr16-49669796;