chr3-52706092-C-G

Variant names:

• chr3-52706092-C-G
• rs779115533
• ENST00000233025.11:c.47C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78

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]

GLT8D1 (HGNC:24870): (glycosyltransferase 8 domain containing 1) This gene encodes a member of the glycosyltransferase family. The specific function of this protein has not been determined. Alternative splicing results in multiple transcript variants of this gene [provided by RefSeq, May 2013]

ACMG classification

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
SPCS1	NM_014041.5	c.-155C>G		upstream_gene_variant		ENST00000619898.5	NP_054760.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPCS1	ENST00000619898.5	c.-155C>G		upstream_gene_variant		1	NM_014041.5	ENSP00000478310.2

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

Other links and lift over

dbSNP: rs779115533; hg19: chr3-52740108;