10-47368324-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_153034.4(ZNF488):c.506G>A(p.Arg169Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,614,174 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 0.00025 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000045 ( 0 hom. )
Consequence
ZNF488
NM_153034.4 missense
NM_153034.4 missense
Scores
1
6
Clinical Significance
Conservation
PhyloP100: 1.39
Genes affected
ZNF488 (HGNC:23535): (zinc finger protein 488) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be involved in oligodendrocyte development; positive regulation of myelination; and regulation of transcription, DNA-templated. Predicted to act upstream of or within negative regulation of transcription, DNA-templated and positive regulation of oligodendrocyte differentiation. 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=0.07232711).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF488 | NM_153034.4 | c.506G>A | p.Arg169Gln | missense_variant | 2/2 | ENST00000585316.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF488 | ENST00000585316.3 | c.506G>A | p.Arg169Gln | missense_variant | 2/2 | 1 | NM_153034.4 | A2 | |
ZNF488 | ENST00000591025.1 | c.185G>A | p.Arg62Gln | missense_variant | 3/3 | 1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000250 AC: 38AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251408Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135898
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GnomAD4 exome AF: 0.0000451 AC: 66AN: 1461852Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23AN XY: 727224
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GnomAD4 genome ? AF: 0.000249 AC: 38AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74474
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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 | Aug 01, 2022 | The c.506G>A (p.R169Q) alteration is located in exon 2 (coding exon 1) of the ZNF488 gene. This alteration results from a G to A substitution at nucleotide position 506, causing the arginine (R) at amino acid position 169 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_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
Sift4G
Benign
T;T
Vest4
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