3-39407646-T-C

Variant names:

• chr3-39407646-T-C
• rs1803893
• ENST00000475346.1:n.73T>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000475346.1(RPSA):​n.73T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,581,046 control chromosomes in the GnomAD database, including 193,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19015 hom., cov: 32)
  • Exomes 𝑓: 0.49 (174618 hom.)
• Consequence: RPSA ENST00000475346.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.34
• Publications: 20 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 3-39407646-T-C is Benign according to our data. Variant chr3-39407646-T-C is described in ClinVar as Benign. ClinVar VariationId is 403395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPSA	NM_002295.6	c.-8T>C		5_prime_UTR_variant	Exon 2 of 7	ENST00000301821.11	NP_002286.2
RPSA	NM_001304288.2	c.-8T>C		5_prime_UTR_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.-8T>C		5_prime_UTR_variant	Exon 2 of 7	1	NM_002295.6	ENSP00000346067.4

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75272 AN: 151926 Hom.: 18981 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.491

GnomAD2 exomes AF: 0.460 AC: 107557 AN: 233646 AF XY: 0.460

Gnomad AFR exome AF: 0.524

Gnomad AMR exome AF: 0.427

Gnomad ASJ exome AF: 0.557

Gnomad EAS exome AF: 0.300

Gnomad FIN exome AF: 0.440

Gnomad NFE exome AF: 0.506

Gnomad OTH exome AF: 0.488

GnomAD4 exome AF: 0.489 AC: 699472 AN: 1429002 Hom.: 174618 Cov.: 32 AF XY: 0.486 AC XY: 345893 AN XY: 712156

African (AFR) AF: 0.529 AC: 17548 AN: 33144

American (AMR) AF: 0.431 AC: 19253 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 14617 AN: 26014

East Asian (EAS) AF: 0.334 AC: 13242 AN: 39610

South Asian (SAS) AF: 0.376 AC: 32271 AN: 85906

European-Finnish (FIN) AF: 0.438 AC: 16654 AN: 37994

Middle Eastern (MID) AF: 0.451 AC: 2444 AN: 5420

European-Non Finnish (NFE) AF: 0.505 AC: 554202 AN: 1096528

Other (OTH) AF: 0.490 AC: 29241 AN: 59692

GnomAD4 genome AF: 0.496 AC: 75360 AN: 152044 Hom.: 19015 Cov.: 32 AF XY: 0.489 AC XY: 36346 AN XY: 74318

African (AFR) AF: 0.533 AC: 22114 AN: 41456

American (AMR) AF: 0.469 AC: 7166 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1941 AN: 3466

East Asian (EAS) AF: 0.330 AC: 1707 AN: 5170

South Asian (SAS) AF: 0.382 AC: 1843 AN: 4822

European-Finnish (FIN) AF: 0.429 AC: 4524 AN: 10550

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34529 AN: 67990

Other (OTH) AF: 0.490 AC: 1034 AN: 2110

Alfa AF: 0.506 Hom.: 7905

Bravo AF: 0.498

Asia WGS AF: 0.365 AC: 1274 AN: 3478

EpiCase AF: 0.503

EpiControl AF: 0.512

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Familial isolated congenital asplenia Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.91
PhyloP100		1.3
Mutation Taster		=300/0	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: rs1803893; hg19: chr3-39449137; COSMIC: COSV57191604; COSMIC: COSV57191604;