1-36420491-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_145047.5(OSCP1):​c.944C>T​(p.Thr315Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OSCP1
NM_145047.5 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.23

Publications

0 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28843045).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OSCP1NM_145047.5 linkc.944C>T p.Thr315Ile missense_variant Exon 8 of 10 ENST00000235532.9 NP_659484.4 Q8WVF1-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OSCP1ENST00000235532.9 linkc.944C>T p.Thr315Ile missense_variant Exon 8 of 10 1 NM_145047.5 ENSP00000235532.5 Q8WVF1-3

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152044
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461740
Hom.:
0
Cov.:
29
AF XY:
0.00000275
AC XY:
2
AN XY:
727186
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33466
American (AMR)
AF:
0.00
AC:
0
AN:
44682
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86240
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111956
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152044
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74242
show subpopulations
African (AFR)
AF:
0.0000242
AC:
1
AN:
41392
American (AMR)
AF:
0.00
AC:
0
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5200
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10566
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68020
Other (OTH)
AF:
0.00
AC:
0
AN:
2084
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 09, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.944C>T (p.T315I) alteration is located in exon 8 (coding exon 8) of the OSCP1 gene. This alteration results from a C to T substitution at nucleotide position 944, causing the threonine (T) at amino acid position 315 to be replaced by an isoleucine (I). 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
0.31
BayesDel_addAF
Benign
-0.049
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.015
.;T;T
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Uncertain
2.8
.;M;.
PhyloP100
5.2
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.7
N;N;N
REVEL
Benign
0.084
Sift
Uncertain
0.028
D;D;D
Sift4G
Uncertain
0.024
D;D;D
Polyphen
0.90
P;P;.
Vest4
0.41
MutPred
0.21
.;Loss of disorder (P = 0.0361);.;
MVP
0.33
MPC
0.27
ClinPred
0.92
D
GERP RS
6.1
Varity_R
0.13
gMVP
0.57
Mutation Taster
=85/15
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

Publications

Other links and lift over

dbSNP: rs1458987459; hg19: chr1-36886092; API