1-36422780-A-G

Variant names:

• chr1-36422780-A-G
• rs1250692472
• NM_145047.5:c.737T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_145047.5(OSCP1):​c.737T>C​(p.Leu246Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L246R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OSCP1 NM_145047.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.37
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSCP1	NM_145047.5	c.737T>C	p.Leu246Pro	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>C	p.Leu246Pro	missense_variant	Exon 6 of 10	1	NM_145047.5	ENSP00000235532.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000413 AC: 1 AN: 241986 AF XY: 0.00000763

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000568

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1438290 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 715188

African (AFR) AF: 0.00 AC: 0 AN: 32706

American (AMR) AF: 0.00 AC: 0 AN: 42670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25362

East Asian (EAS) AF: 0.00 AC: 0 AN: 39010

South Asian (SAS) AF: 0.00 AC: 0 AN: 82386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098548

Other (OTH) AF: 0.00 AC: 0 AN: 59218

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;T;T;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.9	.;M;.;.
PhyloP100		8.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Pathogenic	0.67
Sift	Benign	0.095	T;T;T;T
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.96
MutPred		0.67		.;Gain of loop (P = 0.0166);.;.;
MVP		0.56
MPC		0.73
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.71
gMVP		0.96
Mutation Taster		=20/80	disease causing

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: rs1250692472; hg19: chr1-36888381;