rs12265792

Variant names:

• chr10-42589386-T-C
• rs12265792
• NM_006955.3:c.*3227A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF33B	NM_006955.3	c.*3227A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000359467.8	NP_008886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF33B	ENST00000359467.8	c.*3227A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_006955.3	ENSP00000352444.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.167 AC: 6929 AN: 41476

American (AMR) AF: 0.116 AC: 1771 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3466

East Asian (EAS) AF: 0.0662 AC: 342 AN: 5166

South Asian (SAS) AF: 0.0149 AC: 72 AN: 4830

European-Finnish (FIN) AF: 0.00282 AC: 30 AN: 10626

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0197 AC: 1338 AN: 68024

Other (OTH) AF: 0.0610 AC: 129 AN: 2114

Alfa AF: 0.0333 Hom.: 375

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
PhyloP100		0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs12265792; hg19: chr10-43084834;