chr8-7358311-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001164457.3(ZNF705G):c.568C>A(p.His190Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000479 in 1,607,620 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 0.000020 ( 0 hom., cov: 37)
Exomes 𝑓: 0.000051 ( 0 hom. )
Consequence
ZNF705G
NM_001164457.3 missense
NM_001164457.3 missense
Scores
5
5
9
Clinical Significance
Conservation
PhyloP100: 5.77
Genes affected
ZNF705G (HGNC:37134): (zinc finger protein 705G) 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 Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.962
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF705G | NM_001164457.3 | c.568C>A | p.His190Asn | missense_variant | 7/7 | ENST00000400156.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF705G | ENST00000400156.4 | c.568C>A | p.His190Asn | missense_variant | 7/7 | 2 | NM_001164457.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000200 AC: 3AN: 149668Hom.: 0 Cov.: 37
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000560 AC: 14AN: 250142Hom.: 0 AF XY: 0.0000665 AC XY: 9AN XY: 135392
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GnomAD4 exome AF: 0.0000508 AC: 74AN: 1457952Hom.: 0 Cov.: 35 AF XY: 0.0000496 AC XY: 36AN XY: 725378
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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 | Dec 27, 2023 | The c.568C>A (p.H190N) alteration is located in exon 5 (coding exon 5) of the ZNF705G gene. This alteration results from a C to A substitution at nucleotide position 568, causing the histidine (H) at amino acid position 190 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
N;N
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Pathogenic
D
Vest4
MutPred
Loss of catalytic residue at K191 (P = 0.0525);
MVP
MPC
ClinPred
T
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