chr3-47418189-C-A

Variant summary

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

The NM_012235.4(SCAP):​c.2392G>T​(p.Val798Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SCAP
NM_012235.4 missense

Scores

3
4
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.21

Publications

58 publications found
Variant links:
Genes affected
SCAP (HGNC:30634): (SREBF chaperone) This gene encodes a protein with a sterol sensing domain (SSD) and seven WD domains. In the presence of cholesterol, this protein binds to sterol regulatory element binding proteins (SREBPs) and mediates their transport from the ER to the Golgi. The SREBPs are then proteolytically cleaved and regulate sterol biosynthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

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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=0.38319468).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SCAPNM_012235.4 linkc.2392G>T p.Val798Phe missense_variant Exon 16 of 23 ENST00000265565.10 NP_036367.2 Q12770-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SCAPENST00000265565.10 linkc.2392G>T p.Val798Phe missense_variant Exon 16 of 23 1 NM_012235.4 ENSP00000265565.5 Q12770-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1422896
Hom.:
0
Cov.:
66
AF XY:
0.00
AC XY:
0
AN XY:
704392
African (AFR)
AF:
0.00
AC:
0
AN:
32564
American (AMR)
AF:
0.00
AC:
0
AN:
39354
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25374
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37574
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81428
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48996
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5716
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1092966
Other (OTH)
AF:
0.00
AC:
0
AN:
58924
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Benign
-0.11
CADD
Benign
21
DANN
Uncertain
0.99
Eigen
Uncertain
0.23
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.45
T
M_CAP
Pathogenic
0.61
D
MetaRNN
Benign
0.38
T
MetaSVM
Benign
-0.92
T
PhyloP100
3.2
Sift4G
Pathogenic
0.0
D
Vest4
0.32
MVP
0.42
ClinPred
0.95
D
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.54
Mutation Taster
=56/44
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs12487736; hg19: chr3-47459679; API