17-47809447-T-C

Variant names:

• chr17-47809447-T-C
• NM_145798.3:c.1912A>G

Variant summary

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

The NM_145798.3(OSBPL7):​c.1912A>G​(p.Thr638Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL7 NM_145798.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02

Genes affected

OSBPL7 (HGNC:16387): (oxysterol binding protein like 7) 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. Two transcript variants encoding the same isoform have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL7	NM_145798.3	c.1912A>G	p.Thr638Ala	missense_variant	Exon 19 of 23	ENST00000007414.8	NP_665741.1
OSBPL7	XM_047435292.1	c.1912A>G	p.Thr638Ala	missense_variant	Exon 19 of 23		XP_047291248.1
OSBPL7	XM_047435293.1	c.1858A>G	p.Thr620Ala	missense_variant	Exon 18 of 22		XP_047291249.1
OSBPL7	XR_934362.2	n.2128A>G		non_coding_transcript_exon_variant	Exon 19 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL7	ENST00000007414.8	c.1912A>G	p.Thr638Ala	missense_variant	Exon 19 of 23	1	NM_145798.3	ENSP00000007414.3
OSBPL7	ENST00000613735.4	n.*246-332A>G		intron_variant	Intron 12 of 15	1		ENSP00000479827.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1912A>G (p.T638A) alteration is located in exon 19 (coding exon 18) of the OSBPL7 gene. This alteration results from a A to G substitution at nucleotide position 1912, causing the threonine (T) at amino acid position 638 to be replaced by an alanine (A). 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	0.65
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.95	P;P
Vest4		0.61
MutPred		0.65		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.76
MPC		0.84
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.36

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: chr17-45886813;