chr3-39408599-C-T

Variant names:

• chr3-39408599-C-T
• NM_002295.6:c.134-7C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_002295.6(RPSA):​c.134-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,309,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: RPSA NM_002295.6 splice_region, intron
• Scores: Splicing: ADA: 0.00007622
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.964
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-39408599-C-T is Benign according to our data. Variant chr3-39408599-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2093591.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002295.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPSA	NM_002295.6	MANE Select	c.134-7C>T		splice_region intron	N/A	NP_002286.2
	RPSA	NM_001304288.2		c.134-7C>T		splice_region intron	N/A	NP_001291217.1	A0A0C4DG17
	SNORA6	NR_002325.1		n.*60C>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPSA	ENST00000301821.11	TSL:1 MANE Select	c.134-7C>T		splice_region intron	N/A	ENSP00000346067.4	P08865
	RPSA	ENST00000443003.2	TSL:1	c.134-7C>T		splice_region intron	N/A	ENSP00000389351.1	A0A0C4DG17
	RPSA	ENST00000922536.1		c.134-7C>T		splice_region intron	N/A	ENSP00000592595.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1309816 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 660388

African (AFR) AF: 0.00 AC: 0 AN: 30444

American (AMR) AF: 0.00 AC: 0 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25210

East Asian (EAS) AF: 0.00 AC: 0 AN: 38934

South Asian (SAS) AF: 0.00 AC: 0 AN: 83248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5488

European-Non Finnish (NFE) AF: 0.00000205 AC: 2 AN: 973266

Other (OTH) AF: 0.00 AC: 0 AN: 55336

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.65
PhyloP100		0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000076
dbscSNV1_RF	Benign	0.0
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

hg19: chr3-39450090;