rs4142248

Positions:

• chr19-44384114-T-C

Variant summary

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

The NM_152354.6(ZNF285):​c.*2358A>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 0.0737 in 152,228 control chromosomes in the GnomAD database, including 776 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 0.074 (776 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF285 NM_152354.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715

Genes affected

ZNF285 (HGNC:13079): (zinc finger protein 285) Predicted to enable DNA-binding transcription factor 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF285	NM_152354.6	c.*2358A>G		3_prime_UTR_variant	4/4	ENST00000614994.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF285	ENST00000614994.5	c.*2358A>G		3_prime_UTR_variant	4/4	1	NM_152354.6	P2

Frequencies

GnomAD3 genomes AF: 0.0735 AC: 11187 AN: 152110 Hom.: 768 Cov.: 31

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.0832

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.0875

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

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0737 AC: 11221 AN: 152228 Hom.: 776 Cov.: 31 AF XY: 0.0774 AC XY: 5759 AN XY: 74430

Gnomad4 AFR AF: 0.0564

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.0790

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.0833

Gnomad4 FIN AF: 0.0248

Gnomad4 NFE AF: 0.0471

Gnomad4 OTH AF: 0.0880

Alfa AF: 0.0646 Hom.: 725

Bravo AF: 0.0907

Asia WGS AF: 0.149 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
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: rs4142248; hg19: chr19-44888276;