rs200799739
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001144757.3(SCG5):c.532C>T(p.Arg178Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,612,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
SCG5
NM_001144757.3 stop_gained
NM_001144757.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 2.29
Genes affected
SCG5 (HGNC:10816): (secretogranin V) This gene encodes a secreted chaperone protein that prevents the aggregation of other secreted proteins, including proteins that are associated with neurodegenerative and metabolic disease. The encoded protein may be best known for its role in the trafficking and activation of prohormone convertase PC2 (encoded by Gene ID: 5126). Phosphorylation of the encoded protein has been shown to have an inhibitory effect on its chaperone function. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein. [provided by RefSeq, Feb 2019]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCG5 | NM_001144757.3 | c.532C>T | p.Arg178Ter | stop_gained | 5/6 | ENST00000300175.9 | |
ARHGAP11A-SCG5 | NM_001368319.1 | c.1771C>T | p.Arg591Ter | stop_gained | 13/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCG5 | ENST00000300175.9 | c.532C>T | p.Arg178Ter | stop_gained | 5/6 | 1 | NM_001144757.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152110Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000203 AC: 5AN: 246576Hom.: 0 AF XY: 0.0000299 AC XY: 4AN XY: 133724
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GnomAD4 exome AF: 0.0000329 AC: 48AN: 1460150Hom.: 0 Cov.: 30 AF XY: 0.0000303 AC XY: 22AN XY: 726202
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74434
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary mixed polyposis syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Knight Diagnostic Laboratories, Oregon Health and Sciences University | Aug 13, 2015 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D;D;D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 11
Find out detailed SpliceAI scores and Pangolin per-transcript scores at