rs3772138

Variant names:

• chr3-39408574-C-T
• rs3772138
• NM_002295.6:c.134-32C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.86
• Publications: 17 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]

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 VariationId 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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPSA	NM_002295.6	c.134-32C>T		intron_variant	Intron 2 of 6	ENST00000301821.11	NP_002286.2
RPSA	NM_001304288.2	c.134-32C>T		intron_variant	Intron 2 of 6		NP_001291217.1
SNORA6	NR_002325.1	n.*35C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPSA	ENST00000301821.11	c.134-32C>T		intron_variant	Intron 2 of 6	1	NM_002295.6	ENSP00000346067.4

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40687 AN: 151940 Hom.: 6014 Cov.: 32

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

GnomAD2 exomes AF: 0.294 AC: 73881 AN: 251424 AF XY: 0.296

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 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.: 14 AF XY: 0.308 AC XY: 159766 AN XY: 519416

African (AFR) AF: 0.157 AC: 3865 AN: 24576

American (AMR) AF: 0.287 AC: 12680 AN: 44126

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 8433 AN: 23302

East Asian (EAS) AF: 0.291 AC: 10939 AN: 37582

South Asian (SAS) AF: 0.274 AC: 21105 AN: 77114

European-Finnish (FIN) AF: 0.298 AC: 15851 AN: 53238

Middle Eastern (MID) AF: 0.237 AC: 1158 AN: 4892

European-Non Finnish (NFE) AF: 0.320 AC: 221462 AN: 691976

Other (OTH) AF: 0.304 AC: 13758 AN: 45308

GnomAD4 genome AF: 0.268 AC: 40711 AN: 152058 Hom.: 6025 Cov.: 32 AF XY: 0.267 AC XY: 19880 AN XY: 74320

African (AFR) AF: 0.160 AC: 6660 AN: 41498

American (AMR) AF: 0.287 AC: 4385 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3466

East Asian (EAS) AF: 0.274 AC: 1419 AN: 5174

South Asian (SAS) AF: 0.282 AC: 1361 AN: 4830

European-Finnish (FIN) AF: 0.296 AC: 3114 AN: 10536

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21733 AN: 67974

Other (OTH) AF: 0.260 AC: 549 AN: 2108

Alfa AF: 0.300 Hom.: 2599

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

Submissions by phenotype

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	-0.74
CADD	Benign	3.8
DANN	Benign	0.70
PhyloP100		-1.9
BranchPoint Hunter		0.0
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: rs3772138; hg19: chr3-39450065; COSMIC: COSV57191610; COSMIC: COSV57191610;