chr3-52706092-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000233025.11(SPCS1):​c.47C>G​(p.Ser16Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S16Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

SPCS1
ENST00000233025.11 missense

Scores

2
6
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.78
Variant links:
Genes affected
SPCS1 (HGNC:23401): (signal peptidase complex subunit 1) Predicted to enable peptidase activity and ribosome binding activity. Involved in viral protein processing and virion assembly. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.3077342).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPCS1NM_014041.5 linkc.-155C>G upstream_gene_variant ENST00000619898.5 NP_054760.4 Q9Y6A9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPCS1ENST00000233025.11 linkc.47C>G p.Ser16Cys missense_variant Exon 1 of 4 1 ENSP00000233025.7 Q9Y6A9
SPCS1ENST00000423431.5 linkc.-30-552C>G intron_variant Intron 1 of 3 3 ENSP00000391610.1 C9JBL1
SPCS1ENST00000619898.5 linkc.-155C>G upstream_gene_variant 1 NM_014041.5 ENSP00000478310.2 A0A5F9YFS9
SPCS1ENST00000448693.2 linkn.-17C>G upstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T;T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.51
.;T
M_CAP
Benign
0.053
D
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-0.93
T
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.50
.;N
REVEL
Benign
0.19
Sift
Pathogenic
0.0
.;D
Sift4G
Uncertain
0.058
T;T
Vest4
0.47
MVP
0.67
MPC
1.9
ClinPred
0.96
D
GERP RS
4.7
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs779115533; hg19: chr3-52740108; API