NM_015550.4:c.1984A>T

Variant names:

• chr7-24816653-T-A
• NM_015550.4:c.1984A>T

Variant summary

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

The NM_015550.4(OSBPL3):​c.1984A>T​(p.Met662Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OSBPL3 NM_015550.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.22

Genes affected

OSBPL3 (HGNC:16370): (oxysterol binding protein like 3) 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. The encoded protein is involved in the regulation of cell adhesion and organization of the actin cytoskeleton. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

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=0.38022605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL3	NM_015550.4	c.1984A>T	p.Met662Leu	missense_variant	Exon 18 of 23	ENST00000313367.7	NP_056365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL3	ENST00000313367.7	c.1984A>T	p.Met662Leu	missense_variant	Exon 18 of 23	1	NM_015550.4	ENSP00000315410.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460798 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726802

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.065	T;.;.;.
Eigen	Benign	-0.044
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.59	N;.;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.38	T;T;T;T
Sift4G	Benign	0.48	T;T;T;T
Polyphen		0.024	B;B;B;D
Vest4		0.61
MutPred		0.55		Loss of MoRF binding (P = 0.0924);.;.;.;
MVP		0.33
MPC		0.21
ClinPred		0.79	D
GERP RS		5.6
Varity_R		0.45
gMVP		0.39

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: chr7-24856272;