Variant chr16-49638923-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_001379286.1(ZNF423):c.302-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 1,541,870 control chromosomes in the GnomAD database, including 1,131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.026 ( 96 hom., cov: 33)

Exomes 𝑓: 0.036 ( 1035 hom. )

Consequence

ZNF423
NM_001379286.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.47

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 16-49638923-G-A is Benign according to our data. Variant chr16-49638923-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0263 (4009/152318) while in subpopulation NFE AF= 0.0449 (3051/68024). AF 95% confidence interval is 0.0435. There are 96 homozygotes in gnomad4. There are 1839 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 96 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF423	NM_001379286.1 linkuse as main transcript	c.302-49C>T		intron_variant		ENST00000563137.7	NP_001366215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF423	ENST00000563137.7 linkuse as main transcript	c.302-49C>T		intron_variant		5	NM_001379286.1	ENSP00000455588.3		A0A7P0Q1F0

Frequencies

GnomAD3 genomes

AF:

0.0263

AC:

4009

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00620

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00772

Gnomad ASJ

AF:

0.0380

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.00932

Gnomad FIN

AF:

0.0325

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0448

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.0255

AC:

4490

AN:

176082

Hom.:

AF XY:

0.0259

AC XY:

2402

AN XY:

92700

show subpopulations

Gnomad AFR exome

AF:

0.00587

Gnomad AMR exome

AF:

0.00457

Gnomad ASJ exome

AF:

0.0370

Gnomad EAS exome

AF:

0.000775

Gnomad SAS exome

AF:

0.0133

Gnomad FIN exome

AF:

0.0325

Gnomad NFE exome

AF:

0.0417

Gnomad OTH exome

AF:

0.0225

GnomAD4 exome

AF:

0.0359

AC:

49922

AN:

1389552

Hom.:

1035

Cov.:

AF XY:

0.0355

AC XY:

24194

AN XY:

682004

show subpopulations

Gnomad4 AFR exome

AF:

0.00528

Gnomad4 AMR exome

AF:

0.00538

Gnomad4 ASJ exome

AF:

0.0369

Gnomad4 EAS exome

AF:

0.000496

Gnomad4 SAS exome

AF:

0.0148

Gnomad4 FIN exome

AF:

0.0313

Gnomad4 NFE exome

AF:

0.0415

Gnomad4 OTH exome

AF:

0.0269

GnomAD4 genome

AF:

0.0263

AC:

4009

AN:

152318

Hom.:

Cov.:

AF XY:

0.0247

AC XY:

1839

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00618

Gnomad4 AMR

AF:

0.00771

Gnomad4 ASJ

AF:

0.0380

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.00933

Gnomad4 FIN

AF:

0.0325

Gnomad4 NFE

AF:

0.0449

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0359

Hom.:

Bravo

AF:

0.0224

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.88

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over