5-52800902-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_015946.5(PELO):āc.508A>Cā(p.Lys170Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,682 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 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.0000062 ( 0 hom. )
Consequence
PELO
NM_015946.5 missense
NM_015946.5 missense
Scores
11
7
1
Clinical Significance
Conservation
PhyloP100: 8.22
Genes affected
PELO (HGNC:8829): (pelota mRNA surveillance and ribosome rescue factor) This gene encodes a protein which contains a conserved nuclear localization signal. The encoded protein may have a role in spermatogenesis, cell cycle control, and in meiotic cell division. [provided by RefSeq, Jul 2008]
ITGA1 (HGNC:6134): (integrin subunit alpha 1) This gene encodes the alpha 1 subunit of integrin receptors. This protein heterodimerizes with the beta 1 subunit to form a cell-surface receptor for collagen and laminin. The heterodimeric receptor is involved in cell-cell adhesion and may play a role in inflammation and fibrosis. The alpha 1 subunit contains an inserted (I) von Willebrand factor type I domain which is thought to be involved in collagen binding. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.936
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PELO | NM_015946.5 | c.508A>C | p.Lys170Gln | missense_variant | 2/3 | ENST00000274311.3 | |
ITGA1 | NM_181501.2 | c.61+12488A>C | intron_variant | ENST00000282588.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PELO | ENST00000274311.3 | c.508A>C | p.Lys170Gln | missense_variant | 2/3 | 1 | NM_015946.5 | P1 | |
ITGA1 | ENST00000282588.7 | c.61+12488A>C | intron_variant | 1 | NM_181501.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250476Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135336
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461518Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727042
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74348
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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 08, 2022 | The c.508A>C (p.K170Q) alteration is located in exon 2 (coding exon 1) of the PELO gene. This alteration results from a A to C substitution at nucleotide position 508, causing the lysine (K) at amino acid position 170 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
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of catalytic residue at K170 (P = 0.0055);
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