chr18-24239310-T-A

Position:

• chr18-24239310-T-A

Variant summary

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

The NM_080597.4(OSBPL1A):​c.1354A>T​(p.Thr452Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL1A NM_080597.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.94

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 (HGNC:):

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=0.2899862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL1A	NM_080597.4	c.1354A>T	p.Thr452Ser	missense_variant	16/28	ENST00000319481.8	NP_542164.2
OSBPL1A	NM_001242508.1	c.208A>T	p.Thr70Ser	missense_variant	4/16		NP_001229437.1
OSBPL1A	XM_017025530.2	c.1408A>T	p.Thr470Ser	missense_variant	16/28		XP_016881019.1
OSBPL1A	NM_018030.4	c.-186A>T		5_prime_UTR_variant	2/14		NP_060500.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL1A	ENST00000319481.8	c.1354A>T	p.Thr452Ser	missense_variant	16/28	1	NM_080597.4	ENSP00000320291.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jul 05, 2024

The c.1354A>T (p.T452S) alteration is located in exon 16 (coding exon 15) of the OSBPL1A gene. This alteration results from a A to T substitution at nucleotide position 1354, causing the threonine (T) at amino acid position 452 to be replaced by a serine (S). 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	0.18
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.090
Sift	Uncertain	0.016	D;D
Sift4G	Benign	0.38	T;T
Polyphen		0.0070	B;.
Vest4		0.41
MutPred		0.26		Loss of glycosylation at T452 (P = 0.0422);.;
MVP		0.51
MPC		0.27
ClinPred		0.90	D
GERP RS		5.8
Varity_R		0.21
gMVP		0.12

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: chr18-21819274;