1-36419004-A-G

Variant names:

• chr1-36419004-A-G
• rs1647452038
• NM_145047.5:c.1010T>C

Variant summary

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

The NM_145047.5(OSCP1):​c.1010T>C​(p.Ile337Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,457,754 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: OSCP1 NM_145047.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82

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.1010T>C	p.Ile337Thr	missense_variant	Exon 9 of 10	ENST00000235532.9	NP_659484.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSCP1	ENST00000235532.9	c.1010T>C	p.Ile337Thr	missense_variant	Exon 9 of 10	1	NM_145047.5	ENSP00000235532.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000549 AC: 8 AN: 1457754 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 725468

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000632

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1010T>C (p.I337T) alteration is located in exon 9 (coding exon 9) of the OSCP1 gene. This alteration results from a T to C substitution at nucleotide position 1010, causing the isoleucine (I) at amino acid position 337 to be replaced by a threonine (T). 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	0.84
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.9	.;M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.5	N;N;D
REVEL	Benign	0.27
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;P;.
Vest4		0.68
MVP		0.64
MPC		0.59
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.33
gMVP		0.64

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

LitVar

Other links and lift over

dbSNP: rs1647452038; hg19: chr1-36884605;