chr3-39407707-C-A

Variant names:

• chr3-39407707-C-A
• rs774713610
• NM_002295.6:c.54C>A

Variant summary

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

The NM_002295.6(RPSA):​c.54C>A​(p.Phe18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RPSA NM_002295.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23588306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPSA	NM_002295.6	c.54C>A	p.Phe18Leu	missense_variant	Exon 2 of 7	ENST00000301821.11	NP_002286.2
RPSA	NM_001304288.2	c.54C>A	p.Phe18Leu	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.54C>A	p.Phe18Leu	missense_variant	Exon 2 of 7	1	NM_002295.6	ENSP00000346067.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000429 AC: 1 AN: 232880 Hom.: 0 AF XY: 0.00000779 AC XY: 1 AN XY: 128380

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1441400 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 717774

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: 0.0000116

Gnomad4 FIN exome AF: 0.0000263

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000872 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.26	T;.;T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.49	N;.;.;.
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.3	N;N;N;.
REVEL	Benign	0.19
Sift	Benign	0.94	T;T;T;.
Sift4G	Benign	0.92	T;T;T;T
Polyphen		0.035	B;B;.;.
Vest4		0.80
MutPred		0.60		Loss of methylation at K17 (P = 0.029);Loss of methylation at K17 (P = 0.029);Loss of methylation at K17 (P = 0.029);Loss of methylation at K17 (P = 0.029);
MVP		0.84
MPC		1.4
ClinPred		0.36	T
GERP RS		2.0
Varity_R		0.66
gMVP		0.78

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: rs774713610; hg19: chr3-39449198;