9-133207240-A-G

Position:

• chr9-133207240-A-G

Variant summary

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

The NM_014581.4(OBP2B):​c.374T>C​(p.Met125Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,324 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OBP2B NM_014581.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.967

Genes affected

OBP2B (HGNC:23381): (odorant binding protein 2B) Predicted to enable small molecule binding activity. Predicted to be involved in chemosensory behavior. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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
OBP2B	NM_014581.4	c.374T>C	p.Met125Thr	missense_variant	4/7	ENST00000372034.8	NP_055396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OBP2B	ENST00000372034.8	c.374T>C	p.Met125Thr	missense_variant	4/7	1	NM_014581.4	ENSP00000361104.3
OBP2B	ENST00000618116.4	c.374T>C	p.Met125Thr	missense_variant	4/7	1		ENSP00000484615.1
OBP2B	ENST00000461961.2	n.282T>C		non_coding_transcript_exon_variant	3/6	1
OBP2B	ENST00000473737.5	n.480T>C		non_coding_transcript_exon_variant	5/8	1		ENSP00000434927.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460324 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726582

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Jun 17, 2024

The c.374T>C (p.M125T) alteration is located in exon 4 (coding exon 4) of the OBP2B gene. This alteration results from a T to C substitution at nucleotide position 374, causing the methionine (M) at amino acid position 125 to be replaced by a threonine (T). 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	0.22
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.3
DANN	Benign	0.37
DEOGEN2	Benign	0.025	T;T;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.32	.;T;T
M_CAP	Benign	0.0014	T
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.0	M;M;.
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.9	D;.;.
REVEL	Benign	0.17
Sift	Benign	0.045	D;.;.
Sift4G	Benign	0.25	T;T;T
Polyphen		0.24	B;B;.
Vest4		0.28
MutPred		0.83		Loss of stability (P = 0.0343);Loss of stability (P = 0.0343);Loss of stability (P = 0.0343);
MVP		0.040
MPC		0.20
ClinPred		0.14	T
GERP RS		1.9
Varity_R		0.15
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr9-136082627;