11-121303397-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006918.5(SC5D):c.22G>A(p.Ala8Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,613,728 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 (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
SC5D
NM_006918.5 missense
NM_006918.5 missense
Scores
1
8
9
Clinical Significance
Conservation
PhyloP100: 6.64
Genes affected
SC5D (HGNC:10547): (sterol-C5-desaturase) This gene encodes an enzyme of cholesterol biosynthesis. The encoded protein catalyzes the conversion of lathosterol into 7-dehydrocholesterol. Mutations in this gene have been associated with lathosterolosis. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
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Very rare variant in population databases, with high coverage;
BP4
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Computational evidence support a benign effect (MetaRNN=0.22024608).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SC5D | NM_006918.5 | c.22G>A | p.Ala8Thr | missense_variant | 2/5 | ENST00000264027.9 | |
SC5D | NM_001024956.3 | c.22G>A | p.Ala8Thr | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SC5D | ENST00000264027.9 | c.22G>A | p.Ala8Thr | missense_variant | 2/5 | 1 | NM_006918.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152076Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251270Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135794
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461652Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727144
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74292
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The SC5D p.Ala8Thr variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs141930747) and in control databases in 10 of 251270 chromosomes at a frequency of 0.0000398 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 7 of 10076 chromosomes (freq: 0.000695), Other in 2 of 6130 chromosomes (freq: 0.000326) and European (non-Finnish) in 1 of 113582 chromosomes (freq: 0.000009), but was not observed in the African, Latino, East Asian, European (Finnish), or South Asian populations. The p.Ala8 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T
Sift4G
Uncertain
T;T;T;T
Polyphen
B;B;B;B
Vest4
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