NM_002295.6:c.134-32C>T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 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	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

GnomAD3 exomes AF: 0.294 AC: 73881 AN: 251424 Hom.: 11239 AF XY: 0.296 AC XY: 40244 AN XY: 135896

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

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.: 32 AF XY: 0.267 AC XY: 19880 AN XY: 74320

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

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
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

Other links and lift over

dbSNP: rs3772138; hg19: chr3-39450065; COSMIC: COSV57191610; COSMIC: COSV57191610;