Variant 12-57715924-T-G details in Genebe, Genetics Data Aggregator

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

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]

OS9 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

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

Synonymous conserved (PhyloP=-3.14 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OS9	NM_006812.4 linkuse as main transcript	c.744T>G	p.Pro248=	synonymous_variant	6/15	ENST00000315970.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OS9	ENST00000315970.12 linkuse as main transcript	c.744T>G	p.Pro248=	synonymous_variant	6/15	1	NM_006812.4	P4	Q13438-1
	ENST00000549477.1 linkuse as main transcript	n.534+5053A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00650

AC:

988

AN:

151916

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00651

AC:

989

AN:

152036

Hom.:

Cov.:

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.:

Bravo

AF:

0.00430

Asia WGS

AF:

0.00115

AC:

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 submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

OS9: 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over