rs1689965

Positions:

• chr17-5181468-G-A
• chr17-5181468-G-C

Variant summary

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

The NM_032530.2(ZNF594):​c.*365C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.982 in 152,284 control chromosomes in the GnomAD database, including 73,460 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 0.98 (73460 hom., cov: 31)
  • Exomes 𝑓: 1.0 (727689 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF594 NM_032530.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307

Genes affected

ZNF594 (HGNC:29392): (zinc finger protein 594) 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. 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF594	NM_032530.2	c.*365C>T		3_prime_UTR_variant	2/2	ENST00000575779.2	NP_115919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF594	ENST00000575779.2	c.*365C>T		3_prime_UTR_variant	2/2	3	NM_032530.2	ENSP00000461032	P1
ZNF594	ENST00000399604.4	c.*365C>T		3_prime_UTR_variant	1/1			ENSP00000382513	P1

Frequencies

GnomAD3 genomes AF: 0.982 AC: 149391 AN: 152166 Hom.: 73407 Cov.: 31

Gnomad AFR AF: 0.939

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.999

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.987

GnomAD3 exomes AF: 0.995 AC: 248866 AN: 250214 Hom.: 123794 AF XY: 0.996 AC XY: 135161 AN XY: 135720

Gnomad AFR exome AF: 0.933

Gnomad AMR exome AF: 0.993

Gnomad ASJ exome AF: 0.999

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.998

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.998 AC: 1458495 AN: 1461756 Hom.: 727689 Cov.: 74 AF XY: 0.998 AC XY: 725754 AN XY: 727192

Gnomad4 AFR exome AF: 0.940

Gnomad4 AMR exome AF: 0.993

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.995

GnomAD4 genome AF: 0.982 AC: 149501 AN: 152284 Hom.: 73460 Cov.: 31 AF XY: 0.983 AC XY: 73151 AN XY: 74452

Gnomad4 AFR AF: 0.939

Gnomad4 AMR AF: 0.990

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.987

Alfa AF: 0.993 Hom.: 13205

Bravo AF: 0.979

Asia WGS AF: 0.998 AC: 3470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.9
DANN	Benign	0.76

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: rs1689965; hg19: chr17-5084763;