rs3803667

chr16-49636479-A-Gchr16-49636479-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001379286.1(ZNF423):c.2697T>C(p.Cys899=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,613,386 control chromosomes in the GnomAD database, including 37,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3466 hom., cov: 33)
  • Exomes 𝑓: 0.21 (34115 hom.)
• Consequence: ZNF423 NM_001379286.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0430

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=-0.61).
• BP6: Variant 16-49636479-A-G is Benign according to our data. Variant chr16-49636479-A-G is described in ClinVar as [Benign]. Clinvar id is 260529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.043 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF423	NM_001379286.1	c.2697T>C	p.Cys899=	synonymous_variant	4/8	ENST00000563137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF423	ENST00000563137.7	c.2697T>C	p.Cys899=	synonymous_variant	4/8	5	NM_001379286.1	P1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31868 AN: 151988 Hom.: 3451 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.191

GnomAD3 exomes AF: 0.223 AC: 56054 AN: 251180 Hom.: 7045 AF XY: 0.217 AC XY: 29418 AN XY: 135838

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.356

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.198

Gnomad SAS exome AF: 0.166

Gnomad FIN exome AF: 0.254

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.212 AC: 310268 AN: 1461280 Hom.: 34115 Cov.: 38 AF XY: 0.210 AC XY: 152503 AN XY: 726930

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.343

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.210 AC: 31927 AN: 152106 Hom.: 3466 Cov.: 33 AF XY: 0.209 AC XY: 15516 AN XY: 74362

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.190

Alfa AF: 0.209 Hom.: 4780

Bravo AF: 0.216

Asia WGS AF: 0.180 AC: 627 AN: 3478

EpiCase AF: 0.202

EpiControl AF: 0.201

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Nephronophthisis 14 Benign:2

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

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	0.93
Dann	Benign	0.62

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: rs3803667; hg19: chr16-49670390; COSMIC: COSV52198797;