19-52780882-C-T

Position:

• chr19-52780882-C-T

Variant summary

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

The NM_001321866.4(ZNF600):​c.-321G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,104 control chromosomes in the GnomAD database, including 3,214 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 0.19 (3214 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF600 NM_001321866.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

ZNF600 (HGNC:30951): (zinc finger protein 600) 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. 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF600	NM_001321866.4	c.-321G>A		5_prime_UTR_variant	3/6	ENST00000692063.1	NP_001308795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF600	ENST00000692063.1	c.-321G>A		5_prime_UTR_variant	3/6		NM_001321866.4	ENSP00000509267.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29252 AN: 151984 Hom.: 3197 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.171

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.193 AC: 29308 AN: 152104 Hom.: 3214 Cov.: 32 AF XY: 0.191 AC XY: 14185 AN XY: 74348

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.0957

Gnomad4 EAS AF: 0.0561

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.171

Alfa AF: 0.171 Hom.: 898

Bravo AF: 0.195

Asia WGS AF: 0.129 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.8
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10404486; hg19: chr19-53284135;