rs767995006

Variant names:

• chr12-57715801-C-G
• rs767995006
• NM_006812.4:c.621C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-57715801-C-G
• chr12-57715801-C-T

Variant summary

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

The NM_006812.4(OS9):​c.621C>G​(p.Ile207Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,286 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I207V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OS9 NM_006812.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.07
• 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]

OS9-AS1 (HGNC:58278):

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006812.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OS9	NM_006812.4	MANE Select	c.621C>G	p.Ile207Met	missense	Exon 6 of 15	NP_006803.1	Q13438-1
	OS9	NM_001410980.1		c.621C>G	p.Ile207Met	missense	Exon 6 of 15	NP_001397909.1	A0A8V8TQI8
	OS9	NM_001410978.1		c.621C>G	p.Ile207Met	missense	Exon 6 of 15	NP_001397907.1	A0A8V8TR34

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OS9	ENST00000315970.12	TSL:1 MANE Select	c.621C>G	p.Ile207Met	missense	Exon 6 of 15	ENSP00000318165.7	Q13438-1
	OS9	ENST00000552285.6	TSL:1	c.621C>G	p.Ile207Met	missense	Exon 6 of 14	ENSP00000450010.1	Q13438-2
	OS9	ENST00000856494.1		c.621C>G	p.Ile207Met	missense	Exon 6 of 15	ENSP00000526553.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461286 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726882

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111724

Other (OTH) AF: 0.00 AC: 0 AN: 60354

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	8.1
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.69	D
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.084	N
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		-3.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.52		Gain of disorder (P = 0.0709)
MVP		0.32
MPC		0.95
ClinPred		0.97	D
GERP RS		-5.1
Varity_R		0.55
gMVP		0.60
Mutation Taster		=52/48	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

Other links and lift over

dbSNP: rs767995006; hg19: chr12-58109584;