chrX-91435582-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_080832.3(PABPC5):c.5G>A(p.Gly2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000167 in 1,199,731 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )
Consequence
PABPC5
NM_080832.3 missense
NM_080832.3 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 1.65
Genes affected
PABPC5 (HGNC:13629): (poly(A) binding protein cytoplasmic 5) This gene encodes a protein that binds to the polyA tail found at the 3' end of most eukaryotic mRNAs. It is thought to play a role in the regulation of mRNA metabolic processes in the cytoplasm. This gene is located in a gene-poor region within the X-specific 13d-sY43 subinterval of the chromosome Xq21.3/Yp11.2 homology block. It is located close to translocation breakpoints associated with premature ovarian failure, and is therefore a potential candidate gene for this disorder. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.21875203).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PABPC5 | NM_080832.3 | c.5G>A | p.Gly2Glu | missense_variant | 2/2 | ENST00000312600.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PABPC5 | ENST00000312600.4 | c.5G>A | p.Gly2Glu | missense_variant | 2/2 | 1 | NM_080832.3 | P1 | |
PABPC5 | ENST00000373105.1 | c.-31-457G>A | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000900 AC: 1AN: 111154Hom.: 0 Cov.: 23 AF XY: 0.0000300 AC XY: 1AN XY: 33368
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GnomAD3 exomes AF: 0.00000581 AC: 1AN: 172011Hom.: 0 AF XY: 0.0000173 AC XY: 1AN XY: 57745
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GnomAD4 exome AF: 9.19e-7 AC: 1AN: 1088518Hom.: 0 Cov.: 30 AF XY: 0.00000281 AC XY: 1AN XY: 355702
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GnomAD4 genome AF: 0.00000899 AC: 1AN: 111213Hom.: 0 Cov.: 23 AF XY: 0.0000299 AC XY: 1AN XY: 33437
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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 | Apr 25, 2023 | The c.5G>A (p.G2E) alteration is located in exon 2 (coding exon 1) of the PABPC5 gene. This alteration results from a G to A substitution at nucleotide position 5, causing the glycine (G) at amino acid position 2 to be replaced by a glutamic acid (E). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of solvent accessibility (P = 0.0456);
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