Genetic Variant NM_014041.5:c.244G>C (chr3-52707747-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014041.5(SPCS1):c.244G>C(p.Glu82Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SPCS1
NM_014041.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.05

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]

SPCS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1563786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPCS1	NM_014041.5 link	c.244G>C	p.Glu82Gln	missense_variant	Exon 4 of 4	ENST00000619898.5	NP_054760.4	Q9Y6A9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPCS1	ENST00000619898.5 link	c.244G>C	p.Glu82Gln	missense_variant	Exon 4 of 4	1	NM_014041.5	ENSP00000478310.2	A0A5F9YFS9
SPCS1	ENST00000233025.11 link	c.445G>C	p.Glu149Gln	missense_variant	Exon 4 of 4	1		ENSP00000233025.7	Q9Y6A9
SPCS1	ENST00000423431.5 link	c.178G>C	p.Glu60Gln	missense_variant	Exon 4 of 4	3		ENSP00000391610.1	C9JBL1
SPCS1	ENST00000474945.1 link	n.709G>C		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;T;T

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.81

T;.;T;.

M_CAP

Benign

0.0037

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.4

.;.;.;L

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.0

N;.;N;.

REVEL

Benign

0.18

Sift

Benign

0.33

T;.;T;.

Sift4G

Benign

0.19

T;T;T;T

Vest4

0.080

MVP

0.73

MPC

1.0

ClinPred

0.68

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.48

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over