3-48284943-T-C

Position:

• chr3-48284943-T-C

Variant summary

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

The ENST00000412564.5(ZNF589):​c.224-14012T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,026 control chromosomes in the GnomAD database, including 6,121 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 0.27 (6121 hom., cov: 32)
• Consequence: ZNF589 ENST00000412564.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

Genes affected

ZNF589 (HGNC:16747): (zinc finger protein 589) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.48284943T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF589	ENST00000412564.5	c.224-14012T>C		intron_variant		1		ENSP00000404398.1
ZNF589	ENST00000440261.6	c.467-1303T>C		intron_variant		2		ENSP00000408719.2
ZNF589	ENST00000427617.6	c.224-1303T>C		intron_variant		2		ENSP00000392719.2
ZNF589	ENST00000448461.5	n.*2184-1303T>C		intron_variant		2		ENSP00000404592.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41776 AN: 151908 Hom.: 6120 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.275 AC: 41793 AN: 152026 Hom.: 6121 Cov.: 32 AF XY: 0.271 AC XY: 20116 AN XY: 74330

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.268

Alfa AF: 0.296 Hom.: 3205

Bravo AF: 0.279

Asia WGS AF: 0.213 AC: 741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.1
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6801801; hg19: chr3-48326433;