3-52706124-G-A

Position:

• chr3-52706124-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000233025.11(SPCS1):​c.79G>A​(p.Gly27Ser) 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. 14/18 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: -0.292

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071887314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPCS1	NM_014041.5	c.-123G>A		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	c.-123G>A		5_prime_UTR_variant	1/4	1	NM_014041.5	ENSP00000478310.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1387716 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 684908

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 07, 2022

The c.79G>A (p.G27S) alteration is located in exon 1 (coding exon 1) of the SPCS1 gene. This alteration results from a G to A substitution at nucleotide position 79, causing the glycine (G) at amino acid position 27 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.5
DANN	Benign	0.84
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.40	.;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.39	.;N
REVEL	Benign	0.011
Sift	Benign	0.47	.;T
Sift4G	Benign	0.68	T;T
Vest4		0.075
MVP		0.12
MPC		0.85
ClinPred		0.065	T
GERP RS		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.17

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: chr3-52740140;