3-39407756-G-C

Variant names:

• chr3-39407756-G-C
• rs1381954909
• NM_002295.6:c.103G>C

Variant summary

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

The NM_002295.6(RPSA):​c.103G>C​(p.Glu35Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPSA NM_002295.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.53

Genes affected

RPSA (HGNC:6502): (ribosomal protein SA) Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Many of the effects of laminin are mediated through interactions with cell surface receptors. These receptors include members of the integrin family, as well as non-integrin laminin-binding proteins. This gene encodes a high-affinity, non-integrin family, laminin receptor 1. This receptor has been variously called 67 kD laminin receptor, 37 kD laminin receptor precursor (37LRP) and p40 ribosome-associated protein. The amino acid sequence of laminin receptor 1 is highly conserved through evolution, suggesting a key biological function. It has been observed that the level of the laminin receptor transcript is higher in colon carcinoma tissue and lung cancer cell line than their normal counterparts. Also, there is a correlation between the upregulation of this polypeptide in cancer cells and their invasive and metastatic phenotype. Multiple copies of this gene exist, however, most of them are pseudogenes thought to have arisen from retropositional events. Two alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPSA	NM_002295.6	c.103G>C	p.Glu35Gln	missense_variant	Exon 2 of 7	ENST00000301821.11	NP_002286.2
RPSA	NM_001304288.2	c.103G>C	p.Glu35Gln	missense_variant	Exon 2 of 7		NP_001291217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPSA	ENST00000301821.11	c.103G>C	p.Glu35Gln	missense_variant	Exon 2 of 7	1	NM_002295.6	ENSP00000346067.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	D;.;T;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.0065	T
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.0	N;N;N;.
REVEL	Benign	0.13
Sift	Benign	0.080	T;T;T;.
Sift4G	Benign	0.083	T;T;T;T
Polyphen		0.033	B;B;.;.
Vest4		0.48
MutPred		0.67		Loss of ubiquitination at K40 (P = 0.0573);Loss of ubiquitination at K40 (P = 0.0573);Loss of ubiquitination at K40 (P = 0.0573);Loss of ubiquitination at K40 (P = 0.0573);
MVP		0.44
MPC		1.3
ClinPred		0.91	D
GERP RS		4.8
Varity_R		0.47
gMVP		0.64

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

LitVar

Other links and lift over

dbSNP: rs1381954909; hg19: chr3-39449247;