chr3-47414320-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_012235.4(SCAP):c.3454C>T(p.Arg1152Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,000 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 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
SCAP
NM_012235.4 missense
NM_012235.4 missense
Scores
1
10
7
Clinical Significance
Conservation
PhyloP100: 2.18
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 made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.36556917).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCAP | NM_012235.4 | c.3454C>T | p.Arg1152Trp | missense_variant | 22/23 | ENST00000265565.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCAP | ENST00000265565.10 | c.3454C>T | p.Arg1152Trp | missense_variant | 22/23 | 1 | NM_012235.4 | P1 | |
SCAP | ENST00000648151.1 | c.3454C>T | p.Arg1152Trp | missense_variant | 23/24 | P1 | |||
SCAP | ENST00000320017.10 | c.*2168C>T | 3_prime_UTR_variant, NMD_transcript_variant | 17/18 | 2 | ||||
SCAP | ENST00000441517.6 | c.*2600C>T | 3_prime_UTR_variant, NMD_transcript_variant | 19/20 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152202Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000360 AC: 9AN: 249934Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135456
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GnomAD4 exome AF: 0.0000288 AC: 42AN: 1460798Hom.: 0 Cov.: 32 AF XY: 0.0000303 AC XY: 22AN XY: 726684
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74350
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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 | Apr 18, 2023 | The c.3454C>T (p.R1152W) alteration is located in exon 22 (coding exon 21) of the SCAP gene. This alteration results from a C to T substitution at nucleotide position 3454, causing the arginine (R) at amino acid position 1152 to be replaced by a tryptophan (W). 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
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.
REVEL
Benign
Sift
Uncertain
D;.;.
Sift4G
Uncertain
D;D;.
Polyphen
D;.;D
Vest4
MutPred
Loss of glycosylation at S1151 (P = 0.0611);.;Loss of glycosylation at S1151 (P = 0.0611);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at