8-7358131-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001164457.3(ZNF705G):c.748C>T(p.His250Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,607,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 38)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
ZNF705G
NM_001164457.3 missense
NM_001164457.3 missense
Scores
4
4
11
Clinical Significance
Conservation
PhyloP100: 7.43
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 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=0.13821238).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF705G | NM_001164457.3 | c.748C>T | p.His250Tyr | missense_variant | 7/7 | ENST00000400156.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF705G | ENST00000400156.4 | c.748C>T | p.His250Tyr | missense_variant | 7/7 | 2 | NM_001164457.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000535 AC: 8AN: 149558Hom.: 0 Cov.: 38
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1457904Hom.: 0 Cov.: 153 AF XY: 0.0000152 AC XY: 11AN XY: 725366
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GnomAD4 genome AF: 0.0000534 AC: 8AN: 149678Hom.: 0 Cov.: 38 AF XY: 0.0000410 AC XY: 3AN XY: 73202
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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 | Jun 01, 2022 | The c.748C>T (p.H250Y) alteration is located in exon 5 (coding exon 5) of the ZNF705G gene. This alteration results from a C to T substitution at nucleotide position 748, causing the histidine (H) at amino acid position 250 to be replaced by a tyrosine (Y). 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
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Vest4
MutPred
Loss of disorder (P = 0.0359);
MVP
MPC
ClinPred
D
GERP RS
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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