NM_006955.3:c.250+1477C>A

Variant names:

• chr10-42630452-G-T
• rs12256867
• NM_006955.3:c.250+1477C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006955.3(ZNF33B):​c.250+1477C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,042 control chromosomes in the GnomAD database, including 1,812 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 0.13 (1812 hom., cov: 32)
• Consequence: ZNF33B NM_006955.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF33B	NM_006955.3	c.250+1477C>A		intron_variant	Intron 4 of 4	ENST00000359467.8	NP_008886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF33B	ENST00000359467.8	c.250+1477C>A		intron_variant	Intron 4 of 4	1	NM_006955.3	ENSP00000352444.2
ZNF33B	ENST00000613419.4	c.250+1477C>A		intron_variant	Intron 3 of 3	5		ENSP00000481265.1
ZNF33B	ENST00000465206.5	c.169+1477C>A		intron_variant	Intron 2 of 3	3		ENSP00000480979.1
ZNF33B	ENST00000486187.5	n.229+1477C>A		intron_variant	Intron 3 of 5	2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20130 AN: 151924 Hom.: 1805 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.0664

Gnomad SAS AF: 0.0247

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.133 AC: 20163 AN: 152042 Hom.: 1812 Cov.: 32 AF XY: 0.128 AC XY: 9548 AN XY: 74324

African (AFR) AF: 0.256 AC: 10596 AN: 41432

American (AMR) AF: 0.164 AC: 2508 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0813 AC: 282 AN: 3468

East Asian (EAS) AF: 0.0662 AC: 343 AN: 5180

South Asian (SAS) AF: 0.0243 AC: 117 AN: 4818

European-Finnish (FIN) AF: 0.0583 AC: 617 AN: 10582

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0771 AC: 5241 AN: 67986

Other (OTH) AF: 0.117 AC: 247 AN: 2110

Alfa AF: 0.117 Hom.: 190

Bravo AF: 0.153

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.49
PhyloP100		-0.56
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: rs12256867; hg19: chr10-43125900;