chr10-133310225-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_145806.4(ZNF511):āc.491A>Gā(p.His164Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,986 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 (ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 33)
Exomes š: 0.000025 ( 0 hom. )
Consequence
ZNF511
NM_145806.4 missense
NM_145806.4 missense
Scores
11
5
3
Clinical Significance
Conservation
PhyloP100: 8.51
Genes affected
ZNF511 (HGNC:28445): (zinc finger protein 511) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]
TUBGCP2 (HGNC:18599): (tubulin gamma complex component 2) Predicted to enable gamma-tubulin binding activity. Predicted to contribute to microtubule minus-end binding activity. Involved in brain development and neuron migration. Located in centrosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.833
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF511 | NM_145806.4 | c.491A>G | p.His164Arg | missense_variant | 4/6 | ENST00000361518.10 | |
ZNF511-PRAP1 | NM_001396060.1 | c.491A>G | p.His164Arg | missense_variant | 4/9 | ||
ZNF511 | NR_130127.2 | n.521A>G | non_coding_transcript_exon_variant | 4/6 | |||
TUBGCP2 | NR_046330.2 | n.718+1395T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF511 | ENST00000361518.10 | c.491A>G | p.His164Arg | missense_variant | 4/6 | 1 | NM_145806.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152266Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251442Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135916
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461720Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727134
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152266Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74392
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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 | Mar 06, 2023 | The c.491A>G (p.H164R) alteration is located in exon 4 (coding exon 4) of the ZNF511 gene. This alteration results from a A to G substitution at nucleotide position 491, causing the histidine (H) at amino acid position 164 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
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Gain of MoRF binding (P = 0.02);Gain of MoRF binding (P = 0.02);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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