3-39412119-C-T

Variant names:

• chr3-39412119-C-T
• rs2723
• NM_002295.6:c.793+58C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002295.6(RPSA):​c.793+58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,518,266 control chromosomes in the GnomAD database, including 180,130 homozygotes. 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: 𝑓 0.39 (14153 hom., cov: 33)
  • Exomes 𝑓: 0.49 (165977 hom.)
• Consequence: RPSA NM_002295.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 11 publications found

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]

RPSA Gene-Disease associations (from GenCC):

• familial isolated congenital asplenia

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002295.6. 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
	RPSA	NM_002295.6	MANE Select	c.793+58C>T		intron	N/A	NP_002286.2
	RPSA	NM_001304288.2		c.808+58C>T		intron	N/A	NP_001291217.1	A0A0C4DG17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPSA	ENST00000301821.11	TSL:1 MANE Select	c.793+58C>T		intron	N/A	ENSP00000346067.4	P08865
	RPSA	ENST00000443003.2	TSL:1	c.808+58C>T		intron	N/A	ENSP00000389351.1	A0A0C4DG17
	RPSA	ENST00000495394.2	TSL:1	n.2791C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59110 AN: 151994 Hom.: 14147 Cov.: 33

Gnomad AFR AF: 0.0980

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.417

GnomAD4 exome AF: 0.487 AC: 664826 AN: 1366154 Hom.: 165977 Cov.: 21 AF XY: 0.488 AC XY: 334587 AN XY: 685486

African (AFR) AF: 0.0836 AC: 2639 AN: 31550

American (AMR) AF: 0.545 AC: 24269 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 10611 AN: 25568

East Asian (EAS) AF: 0.612 AC: 24018 AN: 39226

South Asian (SAS) AF: 0.481 AC: 40519 AN: 84288

European-Finnish (FIN) AF: 0.563 AC: 28479 AN: 50540

Middle Eastern (MID) AF: 0.499 AC: 2787 AN: 5586

European-Non Finnish (NFE) AF: 0.491 AC: 504928 AN: 1027564

Other (OTH) AF: 0.464 AC: 26576 AN: 57270

GnomAD4 genome AF: 0.389 AC: 59114 AN: 152112 Hom.: 14153 Cov.: 33 AF XY: 0.397 AC XY: 29528 AN XY: 74356

African (AFR) AF: 0.0977 AC: 4059 AN: 41526

American (AMR) AF: 0.489 AC: 7481 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1442 AN: 3466

East Asian (EAS) AF: 0.593 AC: 3064 AN: 5166

South Asian (SAS) AF: 0.466 AC: 2249 AN: 4824

European-Finnish (FIN) AF: 0.573 AC: 6044 AN: 10556

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33202 AN: 67964

Other (OTH) AF: 0.419 AC: 886 AN: 2116

Alfa AF: 0.285 Hom.: 870

Bravo AF: 0.372

Asia WGS AF: 0.491 AC: 1706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.58
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs2723; hg19: chr3-39453610; COSMIC: COSV57192709; COSMIC: COSV57192709;