8-89924954-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001126111.3(OSGIN2):c.1072G>A(p.Ala358Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,594 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: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
OSGIN2
NM_001126111.3 missense
NM_001126111.3 missense
Scores
8
8
3
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
OSGIN2 (HGNC:1355): (oxidative stress induced growth inhibitor family member 2) Predicted to enable growth factor activity. Predicted to be involved in negative regulation of cell growth. [provided by Alliance of Genome Resources, Apr 2022]
NBN (HGNC:7652): (nibrin) Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [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, 0.896
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OSGIN2 | NM_001126111.3 | c.1072G>A | p.Ala358Thr | missense_variant | 6/6 | ENST00000451899.7 | NP_001119583.1 | |
OSGIN2 | NM_004337.2 | c.940G>A | p.Ala314Thr | missense_variant | 6/6 | NP_004328.1 | ||
OSGIN2 | XM_011517287.4 | c.940G>A | p.Ala314Thr | missense_variant | 6/6 | XP_011515589.1 | ||
OSGIN2 | XM_011517288.4 | c.541G>A | p.Ala181Thr | missense_variant | 3/3 | XP_011515590.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OSGIN2 | ENST00000451899.7 | c.1072G>A | p.Ala358Thr | missense_variant | 6/6 | 1 | NM_001126111.3 | ENSP00000396445 | ||
OSGIN2 | ENST00000297438.6 | c.940G>A | p.Ala314Thr | missense_variant | 6/6 | 1 | ENSP00000297438 | P1 | ||
OSGIN2 | ENST00000647849.1 | c.940G>A | p.Ala314Thr | missense_variant | 6/6 | ENSP00000497119 | P1 | |||
NBN | ENST00000697292.1 | c.*426C>T | 3_prime_UTR_variant | 17/17 | ENSP00000513229 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250670Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135430
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461594Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727112
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GnomAD4 genome Cov.: 32
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32
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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 | Jan 20, 2023 | The c.1072G>A (p.A358T) alteration is located in exon 6 (coding exon 6) of the OSGIN2 gene. This alteration results from a G to A substitution at nucleotide position 1072, causing the alanine (A) at amino acid position 358 to be replaced by a threonine (T). 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
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D;D
REVEL
Uncertain
Sift
Pathogenic
.;D;D
Sift4G
Uncertain
.;D;D
Polyphen
D;D;D
Vest4
0.86, 0.89
MutPred
Loss of stability (P = 0.1157);Loss of stability (P = 0.1157);.;
MVP
0.59
MPC
1.1
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