19-23145949-A-AT

Position:

• chr19-23145949-A-AT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001277403.2(ZNF730):​c.906dupT​(p.Lys303fs) variant causes a frameshift, stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,608,564 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0037 (20 hom.)
• Consequence: ZNF730 NM_001277403.2 frameshift, stop_gained
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.496

Genes affected

ZNF730 (HGNC:32470): (zinc finger protein 730) 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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 19-23145949-A-AT is Benign according to our data. Variant chr19-23145949-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 2649660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF730	NM_001277403.2	c.906dupT	p.Lys303fs	frameshift_variant, stop_gained	4/4	ENST00000597761.7	NP_001264332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF730	ENST00000597761.7	c.906dupT	p.Lys303fs	frameshift_variant, stop_gained	4/4	5	NM_001277403.2	ENSP00000472959.1

Frequencies

GnomAD3 genomes AF: 0.00287 AC: 437 AN: 152182 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00443

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00353 AC: 855 AN: 242238 Hom.: 8 AF XY: 0.00392 AC XY: 517 AN XY: 131988

Gnomad AFR exome AF: 0.000340

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.00459

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00818

Gnomad FIN exome AF: 0.000346

Gnomad NFE exome AF: 0.00428

Gnomad OTH exome AF: 0.00239

GnomAD4 exome AF: 0.00367 AC: 5343 AN: 1456264 Hom.: 20 Cov.: 33 AF XY: 0.00389 AC XY: 2821 AN XY: 724374

Gnomad4 AFR exome AF: 0.000483

Gnomad4 AMR exome AF: 0.00235

Gnomad4 ASJ exome AF: 0.00425

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00779

Gnomad4 FIN exome AF: 0.000425

Gnomad4 NFE exome AF: 0.00375

Gnomad4 OTH exome AF: 0.00383

GnomAD4 genome AF: 0.00287 AC: 437 AN: 152300 Hom.: 4 Cov.: 33 AF XY: 0.00278 AC XY: 207 AN XY: 74464

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00849

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00443

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00255 Hom.: 0

Bravo AF: 0.00264

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

ZNF730: BS2 -

Computational scores

Source: dbNSFP v4.3

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: rs529180941; hg19: chr19-23328751;