Variant 16-49636614-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001379286.1(ZNF423):c.2562C>A(p.Pro854=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,613,916 control chromosomes in the GnomAD database, including 1,493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 89 hom., cov: 33)

Exomes 𝑓: 0.014 ( 1404 hom. )

Consequence

ZNF423
NM_001379286.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.547

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 16-49636614-G-T is Benign according to our data. Variant chr16-49636614-G-T is described in ClinVar as [Benign]. Clinvar id is 260528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.547 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF423	NM_001379286.1 linkuse as main transcript	c.2562C>A	p.Pro854=	synonymous_variant	4/8	ENST00000563137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF423	ENST00000563137.7 linkuse as main transcript	c.2562C>A	p.Pro854=	synonymous_variant	4/8	5	NM_001379286.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1587

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.00396

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.0277

AC:

6940

AN:

250684

Hom.:

470

AF XY:

0.0332

AC XY:

4499

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00249

Gnomad EAS exome

AF:

0.122

Gnomad SAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.00495

Gnomad NFE exome

AF:

0.00202

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.0136

AC:

19836

AN:

1461736

Hom.:

1404

Cov.:

AF XY:

0.0174

AC XY:

12666

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.00203

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.00452

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.0159

GnomAD4 genome

AF:

0.0104

AC:

1578

AN:

152180

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1019

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.122

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.00396

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00243

Hom.:

Bravo

AF:

0.00743

Asia WGS

AF:

0.101

AC:

351

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00219

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephronophthisis 14

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

Cadd

Benign

0.56

Dann

Benign

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over