3-47414335-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_012235.4(SCAP):c.3439G>A(p.Val1147Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000167 in 1,613,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
SCAP
NM_012235.4 missense
NM_012235.4 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 5.59
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.17647755).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCAP | NM_012235.4 | c.3439G>A | p.Val1147Ile | missense_variant | 22/23 | ENST00000265565.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCAP | ENST00000265565.10 | c.3439G>A | p.Val1147Ile | missense_variant | 22/23 | 1 | NM_012235.4 | P1 | |
SCAP | ENST00000648151.1 | c.3439G>A | p.Val1147Ile | missense_variant | 23/24 | P1 | |||
SCAP | ENST00000320017.10 | c.*2153G>A | 3_prime_UTR_variant, NMD_transcript_variant | 17/18 | 2 | ||||
SCAP | ENST00000441517.6 | c.*2585G>A | 3_prime_UTR_variant, NMD_transcript_variant | 19/20 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152230Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000841 AC: 21AN: 249782Hom.: 0 AF XY: 0.0000886 AC XY: 12AN XY: 135402
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GnomAD4 exome AF: 0.000175 AC: 256AN: 1460826Hom.: 0 Cov.: 32 AF XY: 0.000191 AC XY: 139AN XY: 726694
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GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74366
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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 | Mar 02, 2023 | The c.3439G>A (p.V1147I) alteration is located in exon 22 (coding exon 21) of the SCAP gene. This alteration results from a G to A substitution at nucleotide position 3439, causing the valine (V) at amino acid position 1147 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.
REVEL
Benign
Sift
Benign
T;.;.
Sift4G
Benign
T;D;.
Polyphen
B;.;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at