chr16-49632652-T-C

Variant names:

• chr16-49632652-T-C
• rs1420676
• NM_001379286.1:c.3516+3008A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379286.1(ZNF423):​c.3516+3008A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,998 control chromosomes in the GnomAD database, including 28,137 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (28137 hom., cov: 31)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.45

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF423	NM_001379286.1	c.3516+3008A>G		intron_variant	Intron 4 of 7	ENST00000563137.7	NP_001366215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF423	ENST00000563137.7	c.3516+3008A>G		intron_variant	Intron 4 of 7	5	NM_001379286.1	ENSP00000455588.3

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87626 AN: 151878 Hom.: 28064 Cov.: 31

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.515

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.577 AC: 87768 AN: 151998 Hom.: 28137 Cov.: 31 AF XY: 0.574 AC XY: 42612 AN XY: 74290

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.516

Alfa AF: 0.467 Hom.: 26934

Bravo AF: 0.593

Asia WGS AF: 0.527 AC: 1835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0010
DANN	Benign	0.38

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: rs1420676; hg19: chr16-49666563;