chr19-2934102-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021217.3(ZNF77):c.1025A>G(p.His342Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
ZNF77
NM_021217.3 missense
NM_021217.3 missense
Scores
6
9
4
Clinical Significance
Conservation
PhyloP100: 3.40
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF77 | NM_021217.3 | c.1025A>G | p.His342Arg | missense_variant | 4/4 | ENST00000314531.5 | |
ZNF77 | XM_047439170.1 | c.929A>G | p.His310Arg | missense_variant | 4/4 | ||
ZNF77 | XM_017027081.2 | c.485A>G | p.His162Arg | missense_variant | 3/3 | ||
ZNF77 | XM_047439171.1 | c.485A>G | p.His162Arg | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF77 | ENST00000314531.5 | c.1025A>G | p.His342Arg | missense_variant | 4/4 | 1 | NM_021217.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152030Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251456Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135904
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GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461892Hom.: 0 Cov.: 79 AF XY: 0.0000275 AC XY: 20AN XY: 727248
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152030Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74252
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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 | Feb 03, 2022 | The c.1025A>G (p.H342R) alteration is located in exon 4 (coding exon 4) of the ZNF77 gene. This alteration results from a A to G substitution at nucleotide position 1025, causing the histidine (H) at amino acid position 342 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
Uncertain
T
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.0256);
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