3-52706151-C-T

Variant names:

• chr3-52706151-C-T
• rs950125332
• ENST00000233025.11:c.106C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000233025.11(SPCS1):​c.106C>T​(p.Gln36*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,390,612 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SPCS1 ENST00000233025.11 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T		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.106C>T	p.Gln36*	stop_gained	Exon 1 of 4	ENSP00000233025.7	Q9Y6A9
	SPCS1	ENST00000619898.5	TSL:1 MANE Select	c.-96C>T		5_prime_UTR	Exon 1 of 4	ENSP00000478310.2	A0A5F9YFS9
	SPCS1	ENST00000918254.1		c.-96C>T		5_prime_UTR	Exon 1 of 4	ENSP00000588313.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1390612 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 686620

African (AFR) AF: 0.00 AC: 0 AN: 31644

American (AMR) AF: 0.00 AC: 0 AN: 35824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25190

East Asian (EAS) AF: 0.00 AC: 0 AN: 35878

South Asian (SAS) AF: 0.00 AC: 0 AN: 79592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5244

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079940

Other (OTH) AF: 0.00 AC: 0 AN: 57978

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	6.9
DANN	Uncertain	0.98
Eigen	Benign	-0.089
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.060	N
PhyloP100		0.046
Vest4		0.045
GERP RS		1.1
PromoterAI		0.0075	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=56/144	disease causing (fs/PTC)

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: rs950125332; hg19: chr3-52740167;