rs9304994

Positions:

• chr19-22089941-G-A
• chr19-22089941-G-C
• chr19-22089941-G-T

Variant summary

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

The NM_033468.4(ZNF257):​c.*499G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 156,190 control chromosomes in the GnomAD database, including 34,872 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 0.66 (33973 hom., cov: 33)
  • Exomes 𝑓: 0.64 (899 hom.)
• Consequence: ZNF257 NM_033468.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

Genes affected

ZNF257 (HGNC:13498): (zinc finger protein 257) 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, DNA-templated. Predicted to be located 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF257	NM_033468.4	c.*499G>A		3_prime_UTR_variant	4/4	ENST00000594947.6	NP_258429.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF257	ENST00000594947.6	c.*499G>A		3_prime_UTR_variant	4/4	4	NM_033468.4	ENSP00000470209	P1
ZNF257	ENST00000435820.6	c.*2204G>A		3_prime_UTR_variant, NMD_transcript_variant	5/5	1		ENSP00000406147
ZNF257	ENST00000651332.1	c.*2002G>A		3_prime_UTR_variant	5/5			ENSP00000498509

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100398 AN: 151782 Hom.: 33927 Cov.: 33

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.651

GnomAD4 exome AF: 0.641 AC: 2750 AN: 4290 Hom.: 899 Cov.: 0 AF XY: 0.641 AC XY: 1458 AN XY: 2274

Gnomad4 AFR exome AF: 0.900

Gnomad4 AMR exome AF: 0.658

Gnomad4 ASJ exome AF: 0.636

Gnomad4 EAS exome AF: 0.619

Gnomad4 SAS exome AF: 0.861

Gnomad4 FIN exome AF: 0.660

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.597

GnomAD4 genome AF: 0.662 AC: 100504 AN: 151900 Hom.: 33973 Cov.: 33 AF XY: 0.667 AC XY: 49492 AN XY: 74216

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.654

Alfa AF: 0.601 Hom.: 23978

Bravo AF: 0.665

Asia WGS AF: 0.782 AC: 2702 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.16

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: rs9304994; hg19: chr19-22272743;