12-57715776-G-T

Variant names:

• chr12-57715776-G-T
• rs113307616
• NM_006812.4:c.596G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006812.4(OS9):​c.596G>T​(p.Gly199Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. G199D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OS9 NM_006812.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.76
• Publications: 1 publications found

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]

ENSG00000257342 (HGNC:58278):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OS9	NM_006812.4	c.596G>T	p.Gly199Val	missense_variant	Exon 6 of 15	ENST00000315970.12	NP_006803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OS9	ENST00000315970.12	c.596G>T	p.Gly199Val	missense_variant	Exon 6 of 15	1	NM_006812.4	ENSP00000318165.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	.;T;.;.;.;.;.;T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.63	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.9	L;L;.;L;.;L;.;.;L
PhyloP100		6.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-4.3	D;D;D;D;D;D;D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.024	D;D;D;D;D;D;D;T;D
Sift4G	Uncertain	0.0040	D;D;D;D;D;D;D;D;D
Polyphen		0.99	.;D;.;.;.;.;.;.;.
Vest4		0.63
MutPred		0.45		Loss of catalytic residue at G199 (P = 0.0611);Loss of catalytic residue at G199 (P = 0.0611);.;Loss of catalytic residue at G199 (P = 0.0611);.;Loss of catalytic residue at G199 (P = 0.0611);.;.;Loss of catalytic residue at G199 (P = 0.0611);
MVP		0.74
MPC		0.50
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.73
gMVP		0.50
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs113307616; hg19: chr12-58109559;