Variant 18-24170442-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_080597.4(OSBPL1A):c.2303T>C(p.Leu768Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OSBPL1A
NM_080597.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Variant links:

Genes affected

OSBPL1A (HGNC:16398): (oxysterol binding protein like 1A) 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, although some members contain only the sterol-binding domain. Transcript variants derived from alternative promoter usage and/or alternative splicing exist; they encode different isoforms. [provided by RefSeq, Jul 2008]

OSBPL1A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.879

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL1A	NM_080597.4 linkuse as main transcript	c.2303T>C	p.Leu768Pro	missense_variant	24/28	ENST00000319481.8	NP_542164.2	Q9BXW6-1B0YJ56B3KU11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OSBPL1A	ENST00000319481.8 linkuse as main transcript	c.2303T>C	p.Leu768Pro	missense_variant	24/28	1	NM_080597.4	ENSP00000320291.3	Q9BXW6-1
OSBPL1A	ENST00000399443.7 linkuse as main transcript	c.764T>C	p.Leu255Pro	missense_variant	10/14	1		ENSP00000382372.3	Q9BXW6-2
OSBPL1A	ENST00000357041.8 linkuse as main transcript	c.1157T>C	p.Leu386Pro	missense_variant	12/16	2		ENSP00000349545.4	Q9BXW6-4
OSBPL1A	ENST00000578013.1 linkuse as main transcript	c.308T>C	p.Leu103Pro	missense_variant	4/8	5		ENSP00000464617.1	J3QSB8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727202

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

The c.2303T>C (p.L768P) alteration is located in exon 24 (coding exon 23) of the OSBPL1A gene. This alteration results from a T to C substitution at nucleotide position 2303, causing the leucine (L) at amino acid position 768 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

0.75

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;.;.;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Benign

0.070

MetaRNN

Pathogenic

0.88

D;D;D;D

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.9

M;.;.;.

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-4.5

D;D;D;.

REVEL

Uncertain

0.55

Sift

Uncertain

0.024

D;D;D;.

Sift4G

Benign

0.13

T;T;T;T

Polyphen

1.0

D;.;.;.

Vest4

0.73

MutPred

0.78

Gain of glycosylation at L768 (P = 0.0253);.;.;.;

MVP

0.70

MPC

2.1

ClinPred

0.99

GERP RS

5.9

Varity_R

0.91

gMVP

0.89

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over