Genetic Variant SPCS1:p.Leu45Pro (chr3-52706179-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000233025.11(SPCS1):c.134T>C(p.Leu45Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPCS1
ENST00000233025.11 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.371

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042393535).

BP6

Variant 3-52706179-T-C is Benign according to our data. Variant chr3-52706179-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2617082.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-68T>C		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.134T>C	p.Leu45Pro	missense	Exon 1 of 4	ENSP00000233025.7	Q9Y6A9
SPCS1	ENST00000619898.5	TSL:1 MANE Select	c.-68T>C		5_prime_UTR	Exon 1 of 4	ENSP00000478310.2	A0A5F9YFS9
GLT8D1	ENST00000858362.1		c.-49A>G		5_prime_UTR	Exon 1 of 10	ENSP00000528421.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000634

AC:

AN:

157708

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000831

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1397984

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

691352

African (AFR)

AF:

0.00

AC:

AN:

32012

American (AMR)

AF:

0.00

AC:

AN:

36844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25276

East Asian (EAS)

AF:

0.00

AC:

AN:

36512

South Asian (SAS)

AF:

0.00

AC:

AN:

80556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5462

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084928

Other (OTH)

AF:

0.00

AC:

AN:

58318

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.040

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.8

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.10

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.14

M_CAP

Benign

0.014

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

PhyloP100

-0.37

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.41

REVEL

Benign

0.15

Sift

Benign

0.33

Sift4G

Uncertain

0.042

Vest4

0.025

MVP

0.13

MPC

1.3

ClinPred

0.089

GERP RS

-4.2

PromoterAI

0.0066

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

gMVP

0.18

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over