rs584630

Positions:

• chr10-38049771-A-C
• chr10-38049771-A-G

Variant summary

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

The NM_006954.2(ZNF33A):​c.251-4604A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,100 control chromosomes in the GnomAD database, including 59,166 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 0.88 (59166 hom., cov: 31)
• Consequence: ZNF33A NM_006954.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

Genes affected

ZNF33A (HGNC:13096): (zinc finger protein 33A) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF33A	NM_006954.2	c.251-4604A>C		intron_variant		ENST00000432900.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF33A	ENST00000432900.7	c.251-4604A>C		intron_variant		1	NM_006954.2	A2

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133937 AN: 151982 Hom.: 59105 Cov.: 31

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.881 AC: 134057 AN: 152100 Hom.: 59166 Cov.: 31 AF XY: 0.883 AC XY: 65607 AN XY: 74330

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.861

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.937

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.861

Gnomad4 OTH AF: 0.863

Alfa AF: 0.871 Hom.: 8196

Bravo AF: 0.873

Asia WGS AF: 0.928 AC: 3222 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.34

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: rs584630; hg19: chr10-38338699;