19-11483833-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_138783.4(ZNF653):c.1697G>A(p.Arg566Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,422,028 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ZNF653
NM_138783.4 missense
NM_138783.4 missense
Scores
2
9
8
Clinical Significance
Conservation
PhyloP100: 5.86
Genes affected
ZNF653 (HGNC:25196): (zinc finger protein 653) Enables AF-2 domain binding activity and transcription corepressor activity. Involved in extracellular negative regulation of signal transduction and negative regulation of nucleic acid-templated transcription. Predicted to be located in extracellular region. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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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 |
---|---|---|---|---|---|---|---|
ZNF653 | NM_138783.4 | c.1697G>A | p.Arg566Gln | missense_variant | 9/9 | ENST00000293771.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF653 | ENST00000293771.10 | c.1697G>A | p.Arg566Gln | missense_variant | 9/9 | 1 | NM_138783.4 | P1 | |
ZNF653 | ENST00000589051.1 | c.190G>A | p.Gly64Ser | missense_variant | 3/3 | 5 | |||
ZNF653 | ENST00000590296.5 | c.270G>A | p.Pro90= | synonymous_variant | 4/4 | 3 | |||
ZNF653 | ENST00000590548.5 | n.1865G>A | non_coding_transcript_exon_variant | 8/8 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000141 AC: 2AN: 1422028Hom.: 0 Cov.: 34 AF XY: 0.00000142 AC XY: 1AN XY: 706298
GnomAD4 exome
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2
AN:
1422028
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Cov.:
34
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1
AN XY:
706298
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
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 | Jan 30, 2024 | The c.1697G>A (p.R566Q) alteration is located in exon 9 (coding exon 9) of the ZNF653 gene. This alteration results from a G to A substitution at nucleotide position 1697, causing the arginine (R) at amino acid position 566 to be replaced by a glutamine (Q). 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
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0464);
MVP
MPC
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