rs774044342

Variant names:

• chr1-36432436-G-A
• rs774044342
• NM_145047.5:c.421C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145047.5(OSCP1):​c.421C>T​(p.Arg141Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,613,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: OSCP1 NM_145047.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36
• Publications: 0 publications found

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]

ENSG00000297367 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145047.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSCP1	NM_145047.5	MANE Select	c.421C>T	p.Arg141Trp	missense	Exon 3 of 10	NP_659484.4
	OSCP1	NM_001330493.2		c.451C>T	p.Arg151Trp	missense	Exon 4 of 11	NP_001317422.1	Q8WVF1-1
	OSCP1	NM_206837.3		c.421C>T	p.Arg141Trp	missense	Exon 3 of 5	NP_996668.1	Q8WVF1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSCP1	ENST00000235532.9	TSL:1 MANE Select	c.421C>T	p.Arg141Trp	missense	Exon 3 of 10	ENSP00000235532.5	Q8WVF1-3
	OSCP1	ENST00000356637.9	TSL:5	c.451C>T	p.Arg151Trp	missense	Exon 4 of 11	ENSP00000349052.5	Q8WVF1-1
	OSCP1	ENST00000955707.1		c.421C>T	p.Arg141Trp	missense	Exon 3 of 10	ENSP00000625766.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251286 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000369 AC: 54 AN: 1461716 Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28 AN XY: 727132

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000477 AC: 53 AN: 1111902

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74306

African (AFR) AF: 0.0000483 AC: 2 AN: 41420

American (AMR) AF: 0.0000655 AC: 1 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000579 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.4
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.015	D
Polyphen		0.98	D
Vest4		0.44
MutPred		0.51		Loss of phosphorylation at T149 (P = 0.0755)
MVP		0.45
MPC		0.15
ClinPred		0.93	D
GERP RS		5.6
Varity_R		0.28
gMVP		0.57
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs774044342; hg19: chr1-36898037;