3-48284943-T-C

Variant names:

• chr3-48284943-T-C
• rs6801801
• ENST00000412564.5:c.224-14012T>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]

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF589	ENST00000412564.5	c.224-14012T>C		intron_variant	Intron 3 of 3	1		ENSP00000404398.1
ZNF589	ENST00000440261.6	c.467-1303T>C		intron_variant	Intron 4 of 4	2		ENSP00000408719.2
ZNF589	ENST00000427617.6	c.224-1303T>C		intron_variant	Intron 3 of 3	2		ENSP00000392719.2
ZNF589	ENST00000448461.5	n.*2184-1303T>C		intron_variant	Intron 4 of 4	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;