3-47414317-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_012235.4(SCAP):c.3457G>C(p.Val1153Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000214 in 1,613,126 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 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 0 hom. )
Consequence
SCAP
NM_012235.4 missense
NM_012235.4 missense
Scores
1
4
13
Clinical Significance
Conservation
PhyloP100: 7.37
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.18537754).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCAP | NM_012235.4 | c.3457G>C | p.Val1153Leu | missense_variant | 22/23 | ENST00000265565.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCAP | ENST00000265565.10 | c.3457G>C | p.Val1153Leu | missense_variant | 22/23 | 1 | NM_012235.4 | P1 | |
SCAP | ENST00000648151.1 | c.3457G>C | p.Val1153Leu | missense_variant | 23/24 | P1 | |||
SCAP | ENST00000320017.10 | c.*2171G>C | 3_prime_UTR_variant, NMD_transcript_variant | 17/18 | 2 | ||||
SCAP | ENST00000441517.6 | c.*2603G>C | 3_prime_UTR_variant, NMD_transcript_variant | 19/20 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152182Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
22
AN:
152182
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000920 AC: 23AN: 249998Hom.: 0 AF XY: 0.0000812 AC XY: 11AN XY: 135504
GnomAD3 exomes
AF:
AC:
23
AN:
249998
Hom.:
AF XY:
AC XY:
11
AN XY:
135504
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000221 AC: 323AN: 1460826Hom.: 0 Cov.: 32 AF XY: 0.000220 AC XY: 160AN XY: 726706
GnomAD4 exome
AF:
AC:
323
AN:
1460826
Hom.:
Cov.:
32
AF XY:
AC XY:
160
AN XY:
726706
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000144 AC: 22AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74466
GnomAD4 genome
?
AF:
AC:
22
AN:
152300
Hom.:
Cov.:
32
AF XY:
AC XY:
10
AN XY:
74466
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
2
ESP6500EA
AF:
AC:
3
ExAC
?
AF:
AC:
7
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2021 | The c.3457G>C (p.V1153L) alteration is located in exon 22 (coding exon 21) of the SCAP gene. This alteration results from a G to C substitution at nucleotide position 3457, causing the valine (V) at amino acid position 1153 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.
REVEL
Benign
Sift
Benign
T;.;.
Sift4G
Benign
T;D;.
Polyphen
P;.;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at