Variant 3-39408574-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002295.6(RPSA):c.134-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,154,172 control chromosomes in the GnomAD database, including 54,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.27 ( 6025 hom., cov: 32)

Exomes 𝑓: 0.31 ( 48556 hom. )

Consequence

RPSA
NM_002295.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.86

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:

SNORA6 (HGNC:32591): (small nucleolar RNA, H/ACA box 6)

SNORA6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 3-39408574-C-T is Benign according to our data. Variant chr3-39408574-C-T is described in ClinVar as [Benign]. Clinvar id is 1327975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
RPSA	NM_002295.6 linkuse as main transcript	c.134-32C>T	intron_variant	ENST00000301821.11
RPSA	NM_001304288.2 linkuse as main transcript	c.134-32C>T	intron_variant
SNORA6	NR_002325.1 linkuse as main transcript		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPSA	ENST00000301821.11 linkuse as main transcript	c.134-32C>T		intron_variant		1	NM_002295.6	P4
SNORA6	ENST00000384033.1 linkuse as main transcript			downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40687

AN:

151940

Hom.:

6014

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.217

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.294

AC:

73881

AN:

251424

Hom.:

11239

AF XY:

0.296

AC XY:

40244

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.288

Gnomad ASJ exome

AF:

0.363

Gnomad EAS exome

AF:

0.251

Gnomad SAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.321

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.309

AC:

309251

AN:

1002114

Hom.:

48556

Cov.:

AF XY:

0.308

AC XY:

159766

AN XY:

519416

show subpopulations

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.287

Gnomad4 ASJ exome

AF:

0.362

Gnomad4 EAS exome

AF:

0.291

Gnomad4 SAS exome

AF:

0.274

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.320

Gnomad4 OTH exome

AF:

0.304

GnomAD4 genome

AF:

0.268

AC:

40711

AN:

152058

Hom.:

6025

Cov.:

AF XY:

0.267

AC XY:

19880

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.287

Gnomad4 ASJ

AF:

0.355

Gnomad4 EAS

AF:

0.274

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.260

Alfa

AF:

0.301

Hom.:

1615

Bravo

AF:

0.260

Asia WGS

AF:

0.259

AC:

903

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

-0.74

CADD

Benign

3.8

DANN

Benign

0.70

BranchPoint Hunter

0.0

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