rs2287313

Variant names:

• chr16-49523530-A-C
• rs2287313
• NM_001379286.1:c.3849+94T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-49523530-A-C
• chr16-49523530-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001379286.1(ZNF423):​c.3849+94T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,034,490 control chromosomes in the GnomAD database, including 162,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (29724 hom., cov: 33)
  • Exomes 𝑓: 0.54 (132372 hom.)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.906
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• nephronophthisis 14

  Inheritance: AD, Unknown, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• Joubert syndrome with oculorenal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-49523530-A-C is Benign according to our data. Variant chr16-49523530-A-C is described in ClinVar as [Benign]. Clinvar id is 1292296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF423	NM_001379286.1	c.3849+94T>G		intron_variant	Intron 7 of 7	ENST00000563137.7	NP_001366215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF423	ENST00000563137.7	c.3849+94T>G		intron_variant	Intron 7 of 7	5	NM_001379286.1	ENSP00000455588.3

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93285 AN: 151932 Hom.: 29672 Cov.: 33

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.617

GnomAD4 exome AF: 0.544 AC: 480154 AN: 882440 Hom.: 132372 AF XY: 0.540 AC XY: 244428 AN XY: 452614

African (AFR) AF: 0.790 AC: 17999 AN: 22780

American (AMR) AF: 0.485 AC: 17977 AN: 37034

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 12126 AN: 19976

East Asian (EAS) AF: 0.489 AC: 17560 AN: 35912

South Asian (SAS) AF: 0.478 AC: 31611 AN: 66116

European-Finnish (FIN) AF: 0.563 AC: 24976 AN: 44396

Middle Eastern (MID) AF: 0.588 AC: 2728 AN: 4636

European-Non Finnish (NFE) AF: 0.544 AC: 332158 AN: 610654

Other (OTH) AF: 0.562 AC: 23019 AN: 40936

GnomAD4 genome AF: 0.614 AC: 93401 AN: 152050 Hom.: 29724 Cov.: 33 AF XY: 0.610 AC XY: 45345 AN XY: 74304

African (AFR) AF: 0.786 AC: 32642 AN: 41510

American (AMR) AF: 0.546 AC: 8333 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2139 AN: 3468

East Asian (EAS) AF: 0.515 AC: 2655 AN: 5154

South Asian (SAS) AF: 0.481 AC: 2312 AN: 4810

European-Finnish (FIN) AF: 0.568 AC: 6007 AN: 10574

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37258 AN: 67948

Other (OTH) AF: 0.622 AC: 1312 AN: 2108

Alfa AF: 0.591 Hom.: 3553

Bravo AF: 0.623

Asia WGS AF: 0.544 AC: 1892 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.66
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2287313; hg19: chr16-49557441; COSMIC: COSV52181801; COSMIC: COSV52181801;