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GeneBe

12-57715924-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_006812.4(OS9):c.744T>G(p.Pro248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00732 in 1,613,030 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0074 ( 52 hom. )

Consequence

OS9
NM_006812.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.14
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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-57715924-T-G is Benign according to our data. Variant chr12-57715924-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2643148.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.14 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OS9NM_006812.4 linkuse as main transcriptc.744T>G p.Pro248= synonymous_variant 6/15 ENST00000315970.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OS9ENST00000315970.12 linkuse as main transcriptc.744T>G p.Pro248= synonymous_variant 6/151 NM_006812.4 P4Q13438-1
ENST00000549477.1 linkuse as main transcriptn.534+5053A>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00650
AC:
988
AN:
151916
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00111
Gnomad AMI
AF:
0.0397
Gnomad AMR
AF:
0.00210
Gnomad ASJ
AF:
0.0101
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00541
Gnomad FIN
AF:
0.0276
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00753
Gnomad OTH
AF:
0.00479
GnomAD3 exomes
AF:
0.00730
AC:
1828
AN:
250268
Hom.:
9
AF XY:
0.00768
AC XY:
1038
AN XY:
135178
show subpopulations
Gnomad AFR exome
AF:
0.000985
Gnomad AMR exome
AF:
0.000870
Gnomad ASJ exome
AF:
0.0106
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00805
Gnomad FIN exome
AF:
0.0238
Gnomad NFE exome
AF:
0.00785
Gnomad OTH exome
AF:
0.00508
GnomAD4 exome
AF:
0.00740
AC:
10817
AN:
1460994
Hom.:
52
Cov.:
32
AF XY:
0.00746
AC XY:
5422
AN XY:
726742
show subpopulations
Gnomad4 AFR exome
AF:
0.00105
Gnomad4 AMR exome
AF:
0.000873
Gnomad4 ASJ exome
AF:
0.0127
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00822
Gnomad4 FIN exome
AF:
0.0240
Gnomad4 NFE exome
AF:
0.00724
Gnomad4 OTH exome
AF:
0.00603
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00651
AC:
989
AN:
152036
Hom.:
6
Cov.:
32
AF XY:
0.00733
AC XY:
545
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00111
Gnomad4 AMR
AF:
0.00209
Gnomad4 ASJ
AF:
0.0101
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00562
Gnomad4 FIN
AF:
0.0276
Gnomad4 NFE
AF:
0.00753
Gnomad4 OTH
AF:
0.00474
Alfa
AF:
0.00675
Hom.:
1
Bravo
AF:
0.00430
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00676
EpiControl
AF:
0.00653

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2022OS9: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
Cadd
Benign
3.9
Dann
Benign
0.66
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.2

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs73125477; hg19: chr12-58109707; COSMIC: COSV57782678; COSMIC: COSV57782678; API