chr19-53237592-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_182609.4(ZNF677):c.1135G>C(p.Glu379Gln) 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. 15/21 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
ZNF677
NM_182609.4 missense
NM_182609.4 missense
Scores
1
14
Clinical Significance
Conservation
PhyloP100: -1.26
Genes affected
ZNF677 (HGNC:28730): (zinc finger protein 677) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. 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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.13474303).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF677 | NM_182609.4 | c.1135G>C | p.Glu379Gln | missense_variant | 5/5 | ENST00000598513.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF677 | ENST00000598513.6 | c.1135G>C | p.Glu379Gln | missense_variant | 5/5 | 1 | NM_182609.4 | P1 | |
ZNF677 | ENST00000333952.8 | c.1135G>C | p.Glu379Gln | missense_variant | 3/3 | 2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 57
GnomAD4 exome
Cov.:
57
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
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 | Dec 17, 2023 | The c.1135G>C (p.E379Q) alteration is located in exon 5 (coding exon 3) of the ZNF677 gene. This alteration results from a G to C substitution at nucleotide position 1135, causing the glutamic acid (E) at amino acid position 379 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
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N
PrimateAI
Benign
T
Sift4G
Uncertain
T;T
Polyphen
P;P
Vest4
MutPred
Gain of ubiquitination at K382 (P = 0.0985);Gain of ubiquitination at K382 (P = 0.0985);
MVP
MPC
0.047
ClinPred
T
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