2-178324178-G-A

Variant names:

• chr2-178324178-G-A
• NM_032523.4:c.104G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_032523.4(OSBPL6):​c.104G>A​(p.Ser35Asn) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OSBPL6 NM_032523.4 missense, splice_region
• Scores: Splicing: ADA: 0.0004254
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33

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 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity OSBL6_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12248406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL6	NM_032523.4	c.104G>A	p.Ser35Asn	missense_variant, splice_region_variant	Exon 4 of 25	ENST00000190611.9	NP_115912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL6	ENST00000190611.9	c.104G>A	p.Ser35Asn	missense_variant, splice_region_variant	Exon 4 of 25	1	NM_032523.4	ENSP00000190611.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1374478 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 675424

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.104G>A (p.S35N) alteration is located in exon 4 (coding exon 2) of the OSBPL6 gene. This alteration results from a G to A substitution at nucleotide position 104, causing the serine (S) at amino acid position 35 to be replaced by an asparagine (N). 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	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.017	.;.;.;.;T;.;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	T;T;T;T;T;.;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.088	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L;L;L;L;L;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.92	N;N;N;N;N;N;N
REVEL	Benign	0.042
Sift	Benign	0.061	T;T;D;T;T;T;T
Sift4G	Benign	0.39	T;T;T;T;T;T;T
Polyphen		0.0	B;B;.;B;B;B;B
Vest4		0.27
MutPred		0.28		Loss of phosphorylation at S35 (P = 0.005);Loss of phosphorylation at S35 (P = 0.005);Loss of phosphorylation at S35 (P = 0.005);Loss of phosphorylation at S35 (P = 0.005);Loss of phosphorylation at S35 (P = 0.005);Loss of phosphorylation at S35 (P = 0.005);.;
MVP		0.068
MPC		0.27
ClinPred		0.48	T
GERP RS		5.0
Varity_R		0.079
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00043
dbscSNV1_RF	Benign	0.13
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: chr2-179188905;