16-83965328-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_182981.3(OSGIN1):c.755C>T(p.Pro252Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000952 in 1,576,066 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 (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000049 ( 0 hom. )
Consequence
OSGIN1
NM_182981.3 missense
NM_182981.3 missense
Scores
2
11
3
Clinical Significance
Conservation
PhyloP100: 4.91
Genes affected
OSGIN1 (HGNC:30093): (oxidative stress induced growth inhibitor 1) This gene encodes an oxidative stress response protein that regulates cell death. Expression of the gene is regulated by p53 and is induced by DNA damage. The protein regulates apoptosis by inducing cytochrome c release from mitochondria. It also appears to be a key regulator of both inflammatory and anti-inflammatory molecules. The loss of this protein correlates with uncontrolled cell growth and tumor formation. Naturally occurring read-through transcription exists between this gene and the neighboring upstream malonyl-CoA decarboxylase (MLYCD) gene, but the read-through transcripts are unlikely to produce a protein product. [provided by RefSeq, Aug 2011]
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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, 0.917
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OSGIN1 | NM_182981.3 | c.755C>T | p.Pro252Leu | missense_variant | 6/6 | ENST00000393306.6 | |
NECAB2 | XM_047434240.1 | c.-23+92C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OSGIN1 | ENST00000393306.6 | c.755C>T | p.Pro252Leu | missense_variant | 6/6 | 1 | NM_182981.3 | P1 | |
OSGIN1 | ENST00000361711.7 | c.755C>T | p.Pro252Leu | missense_variant | 6/6 | 2 | P1 | ||
OSGIN1 | ENST00000343939.6 | n.1387C>T | non_coding_transcript_exon_variant | 7/7 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000139 AC: 3AN: 216538Hom.: 0 AF XY: 0.0000256 AC XY: 3AN XY: 117416
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GnomAD4 exome AF: 0.00000492 AC: 7AN: 1423862Hom.: 0 Cov.: 34 AF XY: 0.00000568 AC XY: 4AN XY: 703970
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN 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 | Jul 28, 2021 | The c.755C>T (p.P252L) alteration is located in exon 6 (coding exon 5) of the OSGIN1 gene. This alteration results from a C to T substitution at nucleotide position 755, causing the proline (P) at amino acid position 252 to be replaced by a leucine (L). 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
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;.
Vest4
MutPred
0.67
.;Loss of disorder (P = 0.0827);.;
MVP
MPC
ClinPred
D
GERP RS
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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