chr9-135547230-C-T

Position:

• chr9-135547230-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014582.3(OBP2A):​c.259C>T​(p.Pro87Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: OBP2A NM_014582.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.498

Genes affected

OBP2A (HGNC:23380): (odorant binding protein 2A) This gene encodes a small extracellular protein belonging to the lipocalin superfamily. The protein is thought to transport small, hydrophobic, volatile molecules or odorants through the nasal mucus to olfactory receptors, and may also function as a scavenger of highly concentrated or toxic odors. The protein is expressed as a monomer in the nasal mucus, and can bind diverse types of odorants with a higher affinity for aldehydes and fatty acids. This gene and a highly similar family member are located in a cluster of lipocalin genes on chromosome 9. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

OBP2A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25079527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OBP2A	NM_014582.3	c.259C>T	p.Pro87Ser	missense_variant	3/7	ENST00000371776.6	NP_055397.1
OBP2A	NM_001293189.2	c.259C>T	p.Pro87Ser	missense_variant	3/7		NP_001280118.1
OBP2A	NM_001293193.2	c.125C>T	p.Ala42Val	missense_variant	2/6		NP_001280122.1
OBP2A	NR_120603.2	n.314C>T		non_coding_transcript_exon_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OBP2A	ENST00000371776.6	c.259C>T	p.Pro87Ser	missense_variant	3/7	1	NM_014582.3	ENSP00000360841.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461280 Hom.: 0 Cov.: 39 AF XY: 0.00000825 AC XY: 6 AN XY: 726918

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.00

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

Sep 25, 2024

The c.259C>T (p.P87S) alteration is located in exon 3 (coding exon 3) of the OBP2A gene. This alteration results from a C to T substitution at nucleotide position 259, causing the proline (P) at amino acid position 87 to be replaced by a serine (S). 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	Benign	0.20
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	-0.032
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.088
Sift	Benign	0.082	T
Sift4G	Benign	0.51	T
Polyphen		1.0	D
Vest4		0.23
MutPred		0.43		Loss of disorder (P = 0.0477);
MVP		0.48
ClinPred		0.97	D
GERP RS		2.5

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: chr9-138439076;