4-271718-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001137608.3(ZNF732):c.1139A>G(p.His380Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000428 in 1,612,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
ZNF732
NM_001137608.3 missense
NM_001137608.3 missense
Scores
1
6
7
Clinical Significance
Conservation
PhyloP100: 3.85
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF732 | NM_001137608.3 | c.1139A>G | p.His380Arg | missense_variant | 4/4 | ENST00000419098.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF732 | ENST00000419098.6 | c.1139A>G | p.His380Arg | missense_variant | 4/4 | 2 | NM_001137608.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000197 AC: 30AN: 152200Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000405 AC: 10AN: 246798Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 134040
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1460678Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 726538
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 01, 2021 | The c.1139A>G (p.H380R) alteration is located in exon 4 (coding exon 4) of the ZNF732 gene. This alteration results from a A to G substitution at nucleotide position 1139, causing the histidine (H) at amino acid position 380 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
N
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
0.27
MVP
MPC
0.022
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at