3-191218916-T-C

Position:

• chr3-191218916-T-C

Variant summary

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

The NM_198184.2(OSTN):​c.272T>C​(p.Leu91Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OSTN NM_198184.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

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:):

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	Protein	UniProt
OSTN	NM_198184.2	c.272T>C	p.Leu91Pro	missense_variant	3/5	ENST00000682035.1	NP_937827.1
OSTN	XM_017006303.3	c.272T>C	p.Leu91Pro	missense_variant	3/5		XP_016861792.1
OSTN-AS1	NR_133663.1	n.255A>G		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSTN	ENST00000682035.1	c.272T>C	p.Leu91Pro	missense_variant	3/5		NM_198184.2	ENSP00000508312.1
OSTN	ENST00000445281.5	c.272T>C	p.Leu91Pro	missense_variant	3/4	5		ENSP00000416576.1
OSTN-AS1	ENST00000430375.1	n.255A>G		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Nov 30, 2022

The c.272T>C (p.L91P) alteration is located in exon 2 (coding exon 2) of the OSTN gene. This alteration results from a T to C substitution at nucleotide position 272, causing the leucine (L) at amino acid position 91 to be replaced by a proline (P). 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	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	.;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-6.6	D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	.;D
Vest4		0.79
MutPred		0.29		Gain of glycosylation at S95 (P = 0.0049);Gain of glycosylation at S95 (P = 0.0049);
MVP		0.076
MPC		0.17
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.95
gMVP		0.21

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-190936705;