dbSNP rs950125332: SPCS1:p.Gln36Glu (chr3-52706151-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000233025.11(SPCS1):c.106C>G(p.Gln36Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,542,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

SPCS1
ENST00000233025.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0460

Publications

0 publications found

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:

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]

GLT8D1 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

GLT8D1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07551643).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000233025.11. 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.-96C>G		5_prime_UTR	Exon 1 of 4	NP_054760.4	A0A5F9YFS9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPCS1	ENST00000233025.11	TSL:1	c.106C>G	p.Gln36Glu	missense	Exon 1 of 4	ENSP00000233025.7	Q9Y6A9
SPCS1	ENST00000619898.5	TSL:1 MANE Select	c.-96C>G		5_prime_UTR	Exon 1 of 4	ENSP00000478310.2	A0A5F9YFS9
SPCS1	ENST00000918254.1		c.-96C>G		5_prime_UTR	Exon 1 of 4	ENSP00000588313.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000205

AC:

AN:

146174

AF XY:

0.0000252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000515

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000273

AC:

AN:

1390612

Hom.:

Cov.:

AF XY:

0.0000204

AC XY:

AN XY:

686620

show subpopulations

African (AFR)

AF:

0.0000316

AC:

AN:

31644

American (AMR)

AF:

0.00

AC:

AN:

35824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25190

East Asian (EAS)

AF:

0.00

AC:

AN:

35878

South Asian (SAS)

AF:

0.00

AC:

AN:

79592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39322

Middle Eastern (MID)

AF:

0.000381

AC:

AN:

5244

European-Non Finnish (NFE)

AF:

0.0000324

AC:

AN:

1079940

Other (OTH)

AF:

0.00

AC:

AN:

57978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000305

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.1

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.086

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.22

M_CAP

Benign

0.012

MetaRNN

Benign

0.076

MetaSVM

Benign

-1.0

PhyloP100

0.046

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.20

REVEL

Benign

0.027

Sift

Benign

0.043

Sift4G

Benign

0.16

Vest4

0.053

MVP

0.29

MPC

0.91

ClinPred

0.040

GERP RS

1.1

PromoterAI

0.013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.078

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over