19-2933806-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_021217.3(ZNF77):c.1321T>G(p.Cys441Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
ZNF77
NM_021217.3 missense
NM_021217.3 missense
Scores
9
5
5
Clinical Significance
Conservation
PhyloP100: 6.55
Genes affected
ZNF77 (HGNC:13150): (zinc finger protein 77) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located 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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.892
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF77 | NM_021217.3 | c.1321T>G | p.Cys441Gly | missense_variant | 4/4 | ENST00000314531.5 | |
ZNF77 | XM_047439170.1 | c.1225T>G | p.Cys409Gly | missense_variant | 4/4 | ||
ZNF77 | XM_017027081.2 | c.781T>G | p.Cys261Gly | missense_variant | 3/3 | ||
ZNF77 | XM_047439171.1 | c.781T>G | p.Cys261Gly | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF77 | ENST00000314531.5 | c.1321T>G | p.Cys441Gly | missense_variant | 4/4 | 1 | NM_021217.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251094Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135682
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460962Hom.: 0 Cov.: 78 AF XY: 0.00000688 AC XY: 5AN XY: 726582
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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 | Nov 15, 2021 | The c.1321T>G (p.C441G) alteration is located in exon 4 (coding exon 4) of the ZNF77 gene. This alteration results from a T to G substitution at nucleotide position 1321, causing the cysteine (C) at amino acid position 441 to be replaced by a glycine (G). 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
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of stability (P = 0.0459);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at