16-49523571-C-T

Position:

• chr16-49523571-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001379286.1(ZNF423):​c.3849+53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,510,192 control chromosomes in the GnomAD database, including 224,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (28056 hom., cov: 34)
  • Exomes 𝑓: 0.54 (196660 hom.)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.70

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 16-49523571-C-T is Benign according to our data. Variant chr16-49523571-C-T is described in ClinVar as [Benign]. Clinvar id is 1245209.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF423	NM_001379286.1	c.3849+53G>A		intron_variant		ENST00000563137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF423	ENST00000563137.7	c.3849+53G>A		intron_variant		5	NM_001379286.1	P1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90771 AN: 152034 Hom.: 28010 Cov.: 34

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.603

GnomAD4 exome AF: 0.536 AC: 727625 AN: 1358040 Hom.: 196660 AF XY: 0.532 AC XY: 362172 AN XY: 680402

Gnomad4 AFR exome AF: 0.759

Gnomad4 AMR exome AF: 0.480

Gnomad4 ASJ exome AF: 0.604

Gnomad4 EAS exome AF: 0.487

Gnomad4 SAS exome AF: 0.462

Gnomad4 FIN exome AF: 0.553

Gnomad4 NFE exome AF: 0.536

Gnomad4 OTH exome AF: 0.549

GnomAD4 genome AF: 0.597 AC: 90880 AN: 152152 Hom.: 28056 Cov.: 34 AF XY: 0.593 AC XY: 44130 AN XY: 74382

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.608

Alfa AF: 0.467 Hom.: 1689

Bravo AF: 0.606

Asia WGS AF: 0.536 AC: 1865 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0010
DANN	Benign	0.78

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: rs2287314; hg19: chr16-49557482; COSMIC: COSV52181807; COSMIC: COSV52181807;