chr19-44274642-CG-C

Variant names:

• chr19-44274642-CG-C
• rs59660444
• NM_001207005.2:c.1983delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_181756.3(ZNF233):​c.1983delG​(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_181756.3 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.53
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181756.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF233	NM_001207005.2	MANE Select	c.1983delG	p.Leu662CysfsTer44	frameshift	Exon 5 of 5	NP_001193934.1
	ZNF233	NM_181756.3		c.1983delG	p.Leu662CysfsTer44	frameshift	Exon 5 of 5	NP_861421.2
	ZNF233	NM_001330529.2		c.*1743delG		3_prime_UTR	Exon 5 of 5	NP_001317458.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF233	ENST00000683810.1	MANE Select	c.1983delG	p.Leu662CysfsTer44	frameshift	Exon 5 of 5	ENSP00000507588.1
	ZNF235	ENST00000589799.5	TSL:1	c.238+24165delC		intron	N/A	ENSP00000468695.1
	ZNF233	ENST00000391958.6	TSL:2	c.1983delG	p.Leu662CysfsTer44	frameshift	Exon 5 of 5	ENSP00000375820.1

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

GnomAD2 exomes AF: 0.198 AC: 48948 AN: 247128 AF XY: 0.181

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 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

African (AFR) AF: 0.606 AC: 20160 AN: 33242

American (AMR) AF: 0.335 AC: 14835 AN: 44298

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 5606 AN: 25810

East Asian (EAS) AF: 0.222 AC: 8802 AN: 39566

South Asian (SAS) AF: 0.119 AC: 10144 AN: 85554

European-Finnish (FIN) AF: 0.136 AC: 7222 AN: 53226

Middle Eastern (MID) AF: 0.245 AC: 1404 AN: 5736

European-Non Finnish (NFE) AF: 0.122 AC: 135224 AN: 1106548

Other (OTH) AF: 0.176 AC: 10589 AN: 60040

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

African (AFR) AF: 0.584 AC: 24069 AN: 41206

American (AMR) AF: 0.309 AC: 4707 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3472

East Asian (EAS) AF: 0.233 AC: 1193 AN: 5124

South Asian (SAS) AF: 0.111 AC: 533 AN: 4820

European-Finnish (FIN) AF: 0.142 AC: 1496 AN: 10572

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.120 AC: 8133 AN: 67972

Other (OTH) AF: 0.254 AC: 534 AN: 2104

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-4.5
Mutation Taster		=126/74	polymorphism (auto)

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

Other links and lift over

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