ENST00000233025.11:c.121C>A

Variant names:

• chr3-52706166-C-A
• rs6617
• ENST00000233025.11:c.121C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000233025.11(SPCS1):​c.121C>A​(p.Pro41Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,393,052 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPCS1 ENST00000233025.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• 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]

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):

• familial amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06411511).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPCS1	NM_014041.5	c.-81C>A		5_prime_UTR_variant	Exon 1 of 4	ENST00000619898.5	NP_054760.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPCS1	ENST00000619898.5	c.-81C>A		5_prime_UTR_variant	Exon 1 of 4	1	NM_014041.5	ENSP00000478310.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1393052 Hom.: 0 Cov.: 58 AF XY: 0.00000145 AC XY: 1 AN XY: 688224

African (AFR) AF: 0.0000315 AC: 1 AN: 31762

American (AMR) AF: 0.00 AC: 0 AN: 36128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25220

East Asian (EAS) AF: 0.00 AC: 0 AN: 36130

South Asian (SAS) AF: 0.00 AC: 0 AN: 79970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38650

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5358

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1081756

Other (OTH) AF: 0.00 AC: 0 AN: 58078

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.46
DANN	Benign	0.87
DEOGEN2	Benign	0.081	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.20	.;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.064	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.050	.;N
REVEL	Benign	0.0070
Sift	Benign	0.14	.;T
Sift4G	Benign	0.40	T;T
Vest4		0.025
MVP		0.21
MPC		0.94
ClinPred		0.064	T
GERP RS		-4.4
PromoterAI		0.047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.13
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs6617; hg19: chr3-52740182;