rs1647776991

Variant names:

• chr1-36423459-A-G
• rs1647776991
• NM_145047.5:c.524T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145047.5(OSCP1):​c.524T>C​(p.Met175Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,452,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OSCP1 NM_145047.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.77

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25978708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSCP1	NM_145047.5	c.524T>C	p.Met175Thr	missense_variant	Exon 5 of 10	ENST00000235532.9	NP_659484.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSCP1	ENST00000235532.9	c.524T>C	p.Met175Thr	missense_variant	Exon 5 of 10	1	NM_145047.5	ENSP00000235532.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1452914 Hom.: 0 Cov.: 30 AF XY: 0.00000415 AC XY: 3 AN XY: 722700

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: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 30, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.524T>C (p.M175T) alteration is located in exon 5 (coding exon 5) of the OSCP1 gene. This alteration results from a T to C substitution at nucleotide position 524, causing the methionine (M) at amino acid position 175 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	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.010	.;T;T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.080
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.71	T;T;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	.;N;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.080	T;T;T;T
Sift4G	Uncertain	0.041	D;D;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.30
MutPred		0.43		.;Gain of sheet (P = 0.0101);.;.;
MVP		0.24
MPC		0.16
ClinPred		0.92	D
GERP RS		4.0
Varity_R		0.13
gMVP		0.70

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: rs1647776991; hg19: chr1-36889060;