3-39407646-T-C

Position:

chr3-39407646-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_002295.6(RPSA):c.-8T>C variant causes a 5 prime UTR 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
NM_002295.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.34

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
RPSA	NM_002295.6 linkuse as main transcript	c.-8T>C		5_prime_UTR_variant	2/7	ENST00000301821.11
RPSA	NM_001304288.2 linkuse as main transcript	c.-8T>C		5_prime_UTR_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPSA	ENST00000301821.11 linkuse as main transcript	c.-8T>C		5_prime_UTR_variant	2/7	1	NM_002295.6	P4

Frequencies

GnomAD3 genomes

AF:

0.495

AC:

75272

AN:

151926

Hom.:

18981

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.460

AC:

107557

AN:

233646

Hom.:

25487

AF XY:

0.460

AC XY:

59049

AN XY:

128450

show subpopulations

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 SAS exome

AF:

0.370

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.:

AF XY:

0.486

AC XY:

345893

AN XY:

712156

show subpopulations

Gnomad4 AFR exome

AF:

0.529

Gnomad4 AMR exome

AF:

0.431

Gnomad4 ASJ exome

AF:

0.562

Gnomad4 EAS exome

AF:

0.334

Gnomad4 SAS exome

AF:

0.376

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.505

Gnomad4 OTH exome

AF:

0.490

GnomAD4 genome

AF:

0.496

AC:

75360

AN:

152044

Hom.:

19015

Cov.:

AF XY:

0.489

AC XY:

36346

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.533

Gnomad4 AMR

AF:

0.469

Gnomad4 ASJ

AF:

0.560

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.382

Gnomad4 FIN

AF:

0.429

Gnomad4 NFE

AF:

0.508

Gnomad4 OTH

AF:

0.490

Alfa

AF:

0.507

Hom.:

5112

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

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Familial isolated congenital asplenia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.91

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over