2-178328299-A-C

Variant names:

• chr2-178328299-A-C
• NM_032523.4:c.239A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032523.4(OSBPL6):​c.239A>C​(p.Gln80Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL6 NM_032523.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.16

Genes affected

OSBPL6 (HGNC:16388): (oxysterol binding protein like 6) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27183318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL6	NM_032523.4	c.239A>C	p.Gln80Pro	missense_variant	Exon 5 of 25	ENST00000190611.9	NP_115912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL6	ENST00000190611.9	c.239A>C	p.Gln80Pro	missense_variant	Exon 5 of 25	1	NM_032523.4	ENSP00000190611.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.239A>C (p.Q80P) alteration is located in exon 5 (coding exon 3) of the OSBPL6 gene. This alteration results from a A to C substitution at nucleotide position 239, causing the glutamine (Q) at amino acid position 80 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	0.91
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;.;.;.;T;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;.;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.27	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L;L;L;L;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.6	D;D;N;D;D;D;D
REVEL	Benign	0.20
Sift	Benign	0.16	T;T;T;T;T;T;T
Sift4G	Benign	0.24	T;T;T;T;T;T;T
Polyphen		1.0	D;D;.;B;D;D;D
Vest4		0.46
MutPred		0.43		Gain of catalytic residue at Q80 (P = 0.0266);Gain of catalytic residue at Q80 (P = 0.0266);Gain of catalytic residue at Q80 (P = 0.0266);Gain of catalytic residue at Q80 (P = 0.0266);Gain of catalytic residue at Q80 (P = 0.0266);Gain of catalytic residue at Q80 (P = 0.0266);.;
MVP		0.13
MPC		1.1
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.56
gMVP		0.71

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: chr2-179193026;