18-14105166-CTTCTCTCCAGTATGGATTCTTTGATGTCGAGTAAGGTGTGAGCCCCTGTTAAAGGCTTTGCCACATTCTTTACATTTGAAGTGT-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_145287.4(ZNF519):c.1290_1373del(p.His431_Lys458del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.011 in 145,194 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (14 hom., cov: 33)
  • Exomes 𝑓: 0.012 (199 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF519 NM_145287.4 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.03

Genes affected

ZNF519 (HGNC:30574): (zinc finger protein 519) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and chromatin 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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_145287.4.
• BP6: Variant 18-14105166-CTTCTCTCCAGTATGGATTCTTTGATGTCGAGTAAGGTGTGAGCCCCTGTTAAAGGCTTTGCCACATTCTTTACATTTGAAGTGT-C is Benign according to our data. Variant chr18-14105166-CTTCTCTCCAGTATGGATTCTTTGATGTCGAGTAAGGTGTGAGCCCCTGTTAAAGGCTTTGCCACATTCTTTACATTTGAAGTGT-C is described in ClinVar as [Benign]. Clinvar id is 788831.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF519	NM_145287.4	c.1290_1373del	p.His431_Lys458del	inframe_deletion	3/3	ENST00000590202.3
ZNF519	NR_033354.2	n.162-20174_162-20091del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF519	ENST00000590202.3	c.1290_1373del	p.His431_Lys458del	inframe_deletion	3/3	1	NM_145287.4	P1
	ENST00000592926.1			non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1605 AN: 145074 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00311

Gnomad AMI AF: 0.0102

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.0384

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00181

Gnomad FIN AF: 0.00726

Gnomad MID AF: 0.0254

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0177

GnomAD3 exomes AF: 0.0112 AC: 2793 AN: 250184 Hom.: 25 AF XY: 0.0115 AC XY: 1562 AN XY: 135330

Gnomad AFR exome AF: 0.00230

Gnomad AMR exome AF: 0.00921

Gnomad ASJ exome AF: 0.0390

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00364

Gnomad FIN exome AF: 0.00625

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.0125

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0124 AC: 18099 AN: 1456872 Hom.: 199 AF XY: 0.0122 AC XY: 8842 AN XY: 724826

Gnomad4 AFR exome AF: 0.00278

Gnomad4 AMR exome AF: 0.00959

Gnomad4 ASJ exome AF: 0.0399

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00402

Gnomad4 FIN exome AF: 0.00591

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.0137

GnomAD4 genome AF: 0.0110 AC: 1602 AN: 145194 Hom.: 14 Cov.: 33 AF XY: 0.0102 AC XY: 724 AN XY: 70824

Gnomad4 AFR AF: 0.00310

Gnomad4 AMR AF: 0.0149

Gnomad4 ASJ AF: 0.0384

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00159

Gnomad4 FIN AF: 0.00726

Gnomad4 NFE AF: 0.0152

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0181 Hom.: 3

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1567947184; hg19: chr18-14105165;