4-271133-T-G

Variant names:

• chr4-271133-T-G
• NM_001137608.3:c.1724A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001137608.3(ZNF732):​c.1724A>C​(p.Gln575Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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)
• Consequence: ZNF732 NM_001137608.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -7.62

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 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=0.12997076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF732	NM_001137608.3	c.1724A>C	p.Gln575Pro	missense_variant	Exon 4 of 4	ENST00000419098.6	NP_001131080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF732	ENST00000419098.6	c.1724A>C	p.Gln575Pro	missense_variant	Exon 4 of 4	2	NM_001137608.3	ENSP00000415774.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1724A>C (p.Q575P) 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 1724, causing the glutamine (Q) at amino acid position 575 to be replaced by a proline (P). 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	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.2
DANN	Benign	0.52
DEOGEN2	Benign	0.0091	.;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.20	T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.3	.;N
REVEL	Benign	0.098
Sift	Benign	0.055	.;T
Sift4G	Benign	0.16	T;T
Polyphen		0.89	.;P
Vest4		0.22
MutPred		0.45		.;Loss of MoRF binding (P = 0.0488);
MVP		0.15
MPC		0.0049
ClinPred		0.12	T
GERP RS		0.98
Varity_R		0.17
gMVP		0.088

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.

Other links and lift over

hg19: chr4-264922;