12-57694838-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006812.4(OS9):​c.251G>A​(p.Arg84His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R84P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

OS9
NM_006812.4 missense

Scores

1
6
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.34

Publications

1 publications found
Variant links:
Genes affected
OS9 (HGNC:16994): (OS9 endoplasmic reticulum lectin) This gene encodes a protein that is highly expressed in osteosarcomas. This protein binds to the hypoxia-inducible factor 1 (HIF-1), a key regulator of the hypoxic response and angiogenesis, and promotes the degradation of one of its subunits. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20231056).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OS9NM_006812.4 linkc.251G>A p.Arg84His missense_variant Exon 2 of 15 ENST00000315970.12 NP_006803.1 Q13438-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OS9ENST00000315970.12 linkc.251G>A p.Arg84His missense_variant Exon 2 of 15 1 NM_006812.4 ENSP00000318165.7 Q13438-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251450
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.37
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
.;T;T;.;T;.;.;.;T;.
Eigen
Uncertain
0.25
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Benign
0.48
N
LIST_S2
Pathogenic
0.98
D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.20
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.0
L;L;.;L;.;L;L;L;.;L
PhyloP100
4.3
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.3
N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.12
Sift
Uncertain
0.019
D;D;T;D;T;D;D;D;T;D
Sift4G
Uncertain
0.045
D;T;D;T;D;D;D;D;D;D
Polyphen
1.0
.;D;.;.;D;.;.;.;.;.
Vest4
0.29
MutPred
0.36
Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);
MVP
0.86
MPC
0.51
ClinPred
0.67
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.33
Mutation Taster
=63/37
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1274307056; hg19: chr12-58088621; API