Variant 3-52706166-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000233025.11(SPCS1):c.121C>G(p.Pro41Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,544,598 control chromosomes in the GnomAD database, including 137,888 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 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: 𝑓 0.46 ( 16111 hom., cov: 31)

Exomes 𝑓: 0.41 ( 121777 hom. )

Consequence

SPCS1
ENST00000233025.11 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.37

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.2408574E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPCS1	NM_014041.5 linkuse as main transcript	c.-81C>G		5_prime_UTR_variant	1/4	ENST00000619898.5	NP_054760.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPCS1	ENST00000619898.5 linkuse as main transcript	c.-81C>G		5_prime_UTR_variant	1/4	1	NM_014041.5	ENSP00000478310	P1

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69102

AN:

151794

Hom.:

16091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.455

GnomAD3 exomes

AF:

0.419

AC:

63083

AN:

150414

Hom.:

13926

AF XY:

0.403

AC XY:

32919

AN XY:

81632

show subpopulations

Gnomad AFR exome

AF:

0.516

Gnomad AMR exome

AF:

0.553

Gnomad ASJ exome

AF:

0.469

Gnomad EAS exome

AF:

0.415

Gnomad SAS exome

AF:

0.268

Gnomad FIN exome

AF:

0.391

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.415

GnomAD4 exome

AF:

0.415

AC:

577608

AN:

1392686

Hom.:

121777

Cov.:

AF XY:

0.409

AC XY:

281686

AN XY:

688004

show subpopulations

Gnomad4 AFR exome

AF:

0.532

Gnomad4 AMR exome

AF:

0.543

Gnomad4 ASJ exome

AF:

0.478

Gnomad4 EAS exome

AF:

0.479

Gnomad4 SAS exome

AF:

0.270

Gnomad4 FIN exome

AF:

0.403

Gnomad4 NFE exome

AF:

0.415

Gnomad4 OTH exome

AF:

0.410

GnomAD4 genome

AF:

0.455

AC:

69177

AN:

151912

Hom.:

16111

Cov.:

AF XY:

0.454

AC XY:

33722

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.522

Gnomad4 AMR

AF:

0.522

Gnomad4 ASJ

AF:

0.466

Gnomad4 EAS

AF:

0.428

Gnomad4 SAS

AF:

0.268

Gnomad4 FIN

AF:

0.398

Gnomad4 NFE

AF:

0.423

Gnomad4 OTH

AF:

0.460

Alfa

AF:

0.411

Hom.:

7982

Bravo

AF:

0.470

TwinsUK

AF:

0.399

AC:

1480

ALSPAC

AF:

0.407

AC:

1569

ExAC

AF:

0.292

AC:

30753

Asia WGS

AF:

0.379

AC:

1317

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.38

DANN

Benign

0.42

DEOGEN2

Benign

0.081

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.19

.;T

MetaRNN

Benign

0.000042

T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

0.25

.;N

REVEL

Benign

0.0070

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Vest4

0.028

MPC

0.82

ClinPred

0.0034

GERP RS

-4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.075

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over