rs12265792

Positions:

• chr10-42589386-T-C

Variant summary

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

The NM_006955.3(ZNF33B):​c.*3227A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 152,178 control chromosomes in the GnomAD database, including 707 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 0.070 (707 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF33B NM_006955.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390

Genes affected

ZNF33B (HGNC:13097): (zinc finger protein 33B) This gene encodes a member of the zinc finger family of proteins. This gene shows decreased expression in cumulus cells derived from patients undergoing controlled ovarian stimulation. This gene is present in a gene cluster with several related zinc finger genes in the pericentromeric region of chromosome 10. Pseudogenes have been identified on chromosomes 7 and 10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF33B	NM_006955.3	c.*3227A>G		3_prime_UTR_variant	5/5	ENST00000359467.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF33B	ENST00000359467.8	c.*3227A>G		3_prime_UTR_variant	5/5	1	NM_006955.3	P4

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10644 AN: 152060 Hom.: 705 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0664

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.00282

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0197

Gnomad OTH AF: 0.0612

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0701 AC: 10662 AN: 152178 Hom.: 707 Cov.: 32 AF XY: 0.0687 AC XY: 5110 AN XY: 74432

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.0662

Gnomad4 SAS AF: 0.0149

Gnomad4 FIN AF: 0.00282

Gnomad4 NFE AF: 0.0197

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0322 Hom.: 171

Bravo AF: 0.0884

Asia WGS AF: 0.0590 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs12265792; hg19: chr10-43084834;