chr4-271314-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001137608.3(ZNF732):c.1543A>G(p.Thr515Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000042 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ZNF732
NM_001137608.3 missense
NM_001137608.3 missense
Scores
14
Clinical Significance
Conservation
PhyloP100: -3.43
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 Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.07848543).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF732 | NM_001137608.3 | c.1543A>G | p.Thr515Ala | missense_variant | 4/4 | ENST00000419098.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF732 | ENST00000419098.6 | c.1543A>G | p.Thr515Ala | missense_variant | 4/4 | 2 | NM_001137608.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 18AN: 150614Hom.: 0 Cov.: 33 FAILED QC
GnomAD3 genomes
?
AF:
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18
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150614
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33
FAILED QC
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GnomAD3 exomes AF: 0.0000431 AC: 10AN: 231924Hom.: 0 AF XY: 0.0000239 AC XY: 3AN XY: 125440
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000422 AC: 61AN: 1446128Hom.: 0 Cov.: 33 AF XY: 0.0000390 AC XY: 28AN XY: 718402
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.000119 AC: 18AN: 150736Hom.: 0 Cov.: 33 AF XY: 0.000163 AC XY: 12AN XY: 73680
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?
Data not reliable, filtered out with message: AS_VQSR
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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 | Aug 04, 2023 | The c.1543A>G (p.T515A) 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 1543, causing the threonine (T) at amino acid position 515 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N
PrimateAI
Benign
T
Sift4G
Benign
T;T
Polyphen
0.0080
.;B
Vest4
0.036
MVP
MPC
0.0054
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at