NM_014041.5:c.205A>C

Variant names:

• chr3-52707708-A-C
• rs1379356068
• NM_014041.5:c.205A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014041.5(SPCS1):​c.205A>C​(p.Ile69Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPCS1 NM_014041.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.44
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3257798).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014041.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPCS1	NM_014041.5	MANE Select	c.205A>C	p.Ile69Leu	missense	Exon 4 of 4	NP_054760.4	A0A5F9YFS9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPCS1	ENST00000619898.5	TSL:1 MANE Select	c.205A>C	p.Ile69Leu	missense	Exon 4 of 4	ENSP00000478310.2	A0A5F9YFS9
	SPCS1	ENST00000233025.11	TSL:1	c.406A>C	p.Ile136Leu	missense	Exon 4 of 4	ENSP00000233025.7	Q9Y6A9
	SPCS1	ENST00000918254.1		c.169A>C	p.Ile57Leu	missense	Exon 4 of 4	ENSP00000588313.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	0.99	L
PhyloP100		8.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.28	N
REVEL	Uncertain	0.32
Sift	Benign	0.45	T
Sift4G	Benign	0.55	T
Vest4		0.33
MVP		0.86
MPC		1.2
ClinPred		0.78	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.67
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1379356068; hg19: chr3-52741724;