Genetic Variant ZNF732:p.Lys584Gln (chr4-271107-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001137608.3(ZNF732):c.1750A>C(p.Lys584Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,358,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

ZNF732
NM_001137608.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Variant links:

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]

ZNF732 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14475241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF732	NM_001137608.3 link	c.1750A>C	p.Lys584Gln	missense_variant	Exon 4 of 4	ENST00000419098.6	NP_001131080.1	B4DXR9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF732	ENST00000419098.6 link	c.1750A>C	p.Lys584Gln	missense_variant	Exon 4 of 4	2	NM_001137608.3	ENSP00000415774.1		B4DXR9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.36e-7

AC:

AN:

1358894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

668490

show subpopulations

Gnomad4 AFR exome

AF:

0.0000350

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1750A>C (p.K584Q) alteration is located in exon 4 (coding exon 4) of the ZNF732 gene. This alteration results from a A to C substitution at nucleotide position 1750, causing the lysine (K) at amino acid position 584 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.046

.;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.34

T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

.;M

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.1

.;N

REVEL

Benign

0.036

Sift

Uncertain

0.0050

.;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.18

.;B

Vest4

0.16

MutPred

0.41

.;Loss of methylation at K584 (P = 0.0043);

MVP

0.040

MPC

0.0055

ClinPred

0.14

GERP RS

0.98

Varity_R

0.17

gMVP

0.0077

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over