chr3-31683938-T-A

Position:

• chr3-31683938-T-A

Variant summary

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

The NM_017784.5(OSBPL10):​c.1422A>T​(p.Leu474Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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)
• Consequence: OSBPL10 NM_017784.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68

Genes affected

OSBPL10 (HGNC:16395): (oxysterol binding protein like 10) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Like most members, the encoded protein contains an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

OSBPL10 (HGNC:):

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=0.1646935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL10	NM_017784.5	c.1422A>T	p.Leu474Phe	missense_variant	8/12	ENST00000396556.7	NP_060254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL10	ENST00000396556.7	c.1422A>T	p.Leu474Phe	missense_variant	8/12	1	NM_017784.5	ENSP00000379804.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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

May 30, 2024

The c.1422A>T (p.L474F) alteration is located in exon 8 (coding exon 8) of the OSBPL10 gene. This alteration results from a A to T substitution at nucleotide position 1422, causing the leucine (L) at amino acid position 474 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	0.27
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.36	N;.
MutationTaster	Benign	0.98	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.097
Sift	Benign	0.12	T;T
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.95	P;.
Vest4		0.23
MutPred		0.47		Loss of glycosylation at K471 (P = 0.0221);.;
MVP		0.41
MPC		0.83
ClinPred		0.76	D
GERP RS		2.6
Varity_R		0.044
gMVP		0.57

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: chr3-31725430;