chr3-52706166-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 14/18 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

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]

ACMG classification

Verdict is Likely_benign. Variant got -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	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

Gnomad4 AFR exome AF: 0.0000315

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.24e-7

Gnomad4 OTH exome AF: 0.00

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
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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-52740182;