rs59660444

chr19-44274642-CG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001207005.2(ZNF233):c.1983del(p.Leu662CysfsTer44) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,605,746 control chromosomes in the GnomAD database, including 29,711 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (8690 hom., cov: 25)
  • Exomes 𝑓: 0.15 (21021 hom.)
• Consequence: ZNF233 NM_001207005.2 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.53

Genes affected

ZNF233 (HGNC:30946): (zinc finger protein 233) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF235 (HGNC:12866): (zinc finger protein 235) This gene product belongs to the zinc finger protein superfamily, members of which are regulatory proteins characterized by nucleic acid-binding zinc finger domains. The encoded protein is a member of the Kruppel family of zinc finger proteins, and contains Kruppel-associated box (KRAB) A and B domains and 15 tandemly arrayed C2H2-type zinc fingers. It is an ortholog of the mouse Zfp93 protein. This gene is located in a cluster of zinc finger genes on 19q13.2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-44274642-CG-C is Benign according to our data. Variant chr19-44274642-CG-C is described in ClinVar as [Benign]. Clinvar id is 403624.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF233	NM_001207005.2	c.1983del	p.Leu662CysfsTer44	frameshift_variant	5/5	ENST00000683810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF233	ENST00000683810.1	c.1983del	p.Leu662CysfsTer44	frameshift_variant	5/5		NM_001207005.2	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41477 AN: 151608 Hom.: 8651 Cov.: 25

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.248

GnomAD3 exomes AF: 0.198 AC: 48948 AN: 247128 Hom.: 6802 AF XY: 0.181 AC XY: 24205 AN XY: 133560

Gnomad AFR exome AF: 0.588

Gnomad AMR exome AF: 0.343

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.234

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.182

GnomAD4 exome AF: 0.147 AC: 213986 AN: 1454020 Hom.: 21021 Cov.: 31 AF XY: 0.145 AC XY: 104729 AN XY: 722466

Gnomad4 AFR exome AF: 0.606

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.274 AC: 41582 AN: 151726 Hom.: 8690 Cov.: 25 AF XY: 0.274 AC XY: 20334 AN XY: 74206

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.254

Alfa AF: 0.0992 Hom.: 227

Bravo AF: 0.306

Asia WGS AF: 0.217 AC: 755 AN: 3478

EpiCase AF: 0.129

EpiControl AF: 0.137

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes:652/2178=29.93% -

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: rs59660444; hg19: chr19-44778795; COSMIC: COSV61933414; COSMIC: COSV61933414;