4-271406-A-C

Variant summary

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

The NM_001137608.3(ZNF732):c.1451T>G(p.Leu484Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000995 in 1,579,276 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (11 hom.)
• Consequence: ZNF732 NM_001137608.3 stop_gained
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.92

Genes affected

ZNF732 (HGNC:37138): (zinc finger protein 732) This gene encodes a kruppel-associated box-containing zinc finger protein (KRAB-ZFP). The encoded protein contains an N-terminal kruppel-associated box (KRAB) domain and sixteen C-terminal C2H2-type zinc finger domains. The KRAB-ZFPs represent the largest family of mammalian transcriptional repressors, which function through the recruitment of the nuclear co-factor KRAB-Associated Protein 1 (KAP1), to engage histone modifiers and induce heterochromatin formation. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM4: Stoplost variant in NM_001137608.3 Downstream stopcodon found after 15 codons.
• BP6: Variant 4-271406-A-C is Benign according to our data. Variant chr4-271406-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3067192.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF732	NM_001137608.3	c.1451T>G	p.Leu484Ter	stop_gained	4/4	ENST00000419098.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF732	ENST00000419098.6	c.1451T>G	p.Leu484Ter	stop_gained	4/4	2	NM_001137608.3	P1

Frequencies

GnomAD3 genomes AF: 0.000647 AC: 85 AN: 131408 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000295

Gnomad ASJ AF: 0.00314

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00567

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00885

Gnomad NFE AF: 0.000639

Gnomad OTH AF: 0.00112

GnomAD3 exomes AF: 0.00152 AC: 349 AN: 229944 Hom.: 7 AF XY: 0.00201 AC XY: 250 AN XY: 124410

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000189

Gnomad ASJ exome AF: 0.00363

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00786

Gnomad FIN exome AF: 0.0000961

Gnomad NFE exome AF: 0.000685

Gnomad OTH exome AF: 0.00157

GnomAD4 exome AF: 0.00103 AC: 1486 AN: 1447754 Hom.: 11 Cov.: 33 AF XY: 0.00127 AC XY: 911 AN XY: 718982

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.000259

Gnomad4 ASJ exome AF: 0.00331

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00859

Gnomad4 FIN exome AF: 0.0000567

Gnomad4 NFE exome AF: 0.000471

Gnomad4 OTH exome AF: 0.00149

GnomAD4 genome AF: 0.000646 AC: 85 AN: 131522 Hom.: 0 Cov.: 32 AF XY: 0.000749 AC XY: 48 AN XY: 64122

Gnomad4 AFR AF: 0.000146

Gnomad4 AMR AF: 0.000295

Gnomad4 ASJ AF: 0.00314

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00568

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000639

Gnomad4 OTH AF: 0.00110

Alfa AF: 0.00139 Hom.: 1

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ExAC AF: 0.00214 AC: 259

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

Mar 01, 2024

ZNF732: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Pathogenic	0.16
Cadd	Uncertain	25
Dann	Benign	0.92
Eigen	Benign	-0.56
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.000050	N
MutationTaster	Benign	1.0	D
Vest4		0.012
GERP RS		-0.71

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: rs201614981; hg19: chr4-265195;