chr1-36423459-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• 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 0 ACMG points.

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

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.524T>C	p.Met175Thr	missense	Exon 5 of 10	NP_659484.4
	OSCP1	NM_001330493.2		c.554T>C	p.Met185Thr	missense	Exon 6 of 11	NP_001317422.1	Q8WVF1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSCP1	ENST00000235532.9	TSL:1 MANE Select	c.524T>C	p.Met175Thr	missense	Exon 5 of 10	ENSP00000235532.5	Q8WVF1-3
	OSCP1	ENST00000356637.9	TSL:5	c.554T>C	p.Met185Thr	missense	Exon 6 of 11	ENSP00000349052.5	Q8WVF1-1
	OSCP1	ENST00000955707.1		c.524T>C	p.Met175Thr	missense	Exon 5 of 10	ENSP00000625766.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33094

American (AMR) AF: 0.00 AC: 0 AN: 43186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25912

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 84902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1107032

Other (OTH) AF: 0.00 AC: 0 AN: 60088

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.080
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		6.8
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.10
Sift	Benign	0.080	T
Sift4G	Uncertain	0.041	D
Polyphen		0.0	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
Mutation Taster		=66/34	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: rs1647776991; hg19: chr1-36889060;