chr3-191218889-G-A

Position:

• chr3-191218889-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198184.2(OSTN):​c.245G>A​(p.Arg82Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSTN NM_198184.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.44

Genes affected

OSTN (HGNC:29961): (osteocrin) Predicted to enable signaling receptor binding activity. Involved in negative regulation of dendrite extension. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

OSTN-AS1 (HGNC:41250): (OSTN antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSTN	NM_198184.2	c.245G>A	p.Arg82Lys	missense_variant	3/5	ENST00000682035.1
OSTN-AS1	NR_133663.1	n.282C>T		non_coding_transcript_exon_variant	4/6
OSTN	XM_017006303.3	c.245G>A	p.Arg82Lys	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSTN	ENST00000682035.1	c.245G>A	p.Arg82Lys	missense_variant	3/5		NM_198184.2	P1
OSTN-AS1	ENST00000430375.1	n.282C>T		non_coding_transcript_exon_variant	4/6	5
OSTN	ENST00000445281.5	c.245G>A	p.Arg82Lys	missense_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2022

The c.245G>A (p.R82K) alteration is located in exon 2 (coding exon 2) of the OSTN gene. This alteration results from a G to A substitution at nucleotide position 245, causing the arginine (R) at amino acid position 82 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	.;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0078	T
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.3	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.87
MutPred		0.31		Gain of glycosylation at S83 (P = 0.0041);Gain of glycosylation at S83 (P = 0.0041);
MVP		0.030
MPC		0.16
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.86
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-190936678; COSMIC: COSV104657326;