ENST00000233025.11:c.110G>A

Variant names:

• chr3-52706155-G-A
• ENST00000233025.11:c.110G>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.110G>A​(p.Cys37Tyr) 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPCS1 ENST00000233025.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.23
• 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):

• 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=0.025936157).

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.-92G>A		5_prime_UTR	Exon 1 of 4	NP_054760.4	A0A5F9YFS9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPCS1	ENST00000233025.11	TSL:1	c.110G>A	p.Cys37Tyr	missense	Exon 1 of 4	ENSP00000233025.7	Q9Y6A9
	SPCS1	ENST00000619898.5	TSL:1 MANE Select	c.-92G>A		5_prime_UTR	Exon 1 of 4	ENSP00000478310.2	A0A5F9YFS9
	SPCS1	ENST00000918254.1		c.-92G>A		5_prime_UTR	Exon 1 of 4	ENSP00000588313.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1391270 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 687030

African (AFR) AF: 0.00 AC: 0 AN: 31672

American (AMR) AF: 0.00 AC: 0 AN: 35870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25192

East Asian (EAS) AF: 0.00 AC: 0 AN: 35920

South Asian (SAS) AF: 0.00 AC: 0 AN: 79676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080354

Other (OTH) AF: 0.00 AC: 0 AN: 58006

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.31
DANN	Benign	0.83
DEOGEN2	Benign	0.081	T
Eigen	Benign	-2.6
Eigen_PC	Benign	-2.6
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.0	T
PhyloP100		-2.2
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.022
Sift	Benign	1.0	T
Sift4G	Benign	0.10	T
Vest4		0.078
MVP		0.25
MPC		1.4
ClinPred		0.073	T
GERP RS		-8.6
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.098
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr3-52740171;