2-178339708-G-T

Variant names:

• chr2-178339708-G-T
• rs1300087261
• NM_032523.4:c.931G>T

Variant summary

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

The NM_032523.4(OSBPL6):​c.931G>T​(p.Val311Phe) 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. 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OSBPL6 NM_032523.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.74

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1730788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL6	NM_032523.4	c.931G>T	p.Val311Phe	missense_variant	Exon 11 of 25	ENST00000190611.9	NP_115912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL6	ENST00000190611.9	c.931G>T	p.Val311Phe	missense_variant	Exon 11 of 25	1	NM_032523.4	ENSP00000190611.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1453398 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722980

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: 0.00

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

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.931G>T (p.V311F) alteration is located in exon 11 (coding exon 9) of the OSBPL6 gene. This alteration results from a G to T substitution at nucleotide position 931, causing the valine (V) at amino acid position 311 to be replaced by a phenylalanine (F). 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	0.23
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Benign	0.020	.;.;T;.;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D;D;T;.;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N;N;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.84	N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.72	T;T;T;T;T
Sift4G	Benign	0.75	T;T;T;T;T
Polyphen		0.43	B;P;P;P;P
Vest4		0.38
MutPred		0.24		Loss of methylation at K309 (P = 0.1253);Loss of methylation at K309 (P = 0.1253);Loss of methylation at K309 (P = 0.1253);Loss of methylation at K309 (P = 0.1253);.;
MVP		0.082
MPC		0.46
ClinPred		0.73	D
GERP RS		5.8
Varity_R		0.32
gMVP		0.21

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

LitVar

Other links and lift over

dbSNP: rs1300087261; hg19: chr2-179204435;