NM_145047.5:c.737T>G

Variant names:

• chr1-36422780-A-C
• NM_145047.5:c.737T>G

Variant summary

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

The NM_145047.5(OSCP1):​c.737T>G​(p.Leu246Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,438,290 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: OSCP1 NM_145047.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.37

Genes affected

OSCP1 (HGNC:29971): (organic solute carrier partner 1) Enables transmembrane transporter activity. Involved in xenobiotic detoxification by transmembrane export across the plasma membrane. Located in basal plasma membrane and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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
OSCP1	NM_145047.5	c.737T>G	p.Leu246Arg	missense_variant	Exon 6 of 10	ENST00000235532.9	NP_659484.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSCP1	ENST00000235532.9	c.737T>G	p.Leu246Arg	missense_variant	Exon 6 of 10	1	NM_145047.5	ENSP00000235532.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438290 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 715188

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: 9.10e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.737T>G (p.L246R) alteration is located in exon 6 (coding exon 6) of the OSCP1 gene. This alteration results from a T to G substitution at nucleotide position 737, causing the leucine (L) at amino acid position 246 to be replaced by an arginine (R). 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	0.69
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	.;T;T;T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.73	D;D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.5	.;M;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Benign	0.093	T;T;T;T
Polyphen		1.0	D;D;.;.
Vest4		0.94
MutPred		0.66		.;Gain of MoRF binding (P = 0.0126);.;.;
MVP		0.54
MPC		0.72
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.78
gMVP		0.96

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: chr1-36888381;