chr3-39407646-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

familial isolated congenital asplenia
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, PanelApp Australia

RPSA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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.-8T>C		5_prime_UTR	Exon 2 of 7	NP_002286.2
	RPSA	NM_001304288.2		c.-8T>C		5_prime_UTR	Exon 2 of 7	NP_001291217.1	A0A0C4DG17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPSA	ENST00000301821.11	TSL:1 MANE Select	c.-8T>C	5_prime_UTR	Exon 2 of 7	ENSP00000346067.4	P08865
RPSA	ENST00000443003.2	TSL:1	c.-8T>C	5_prime_UTR	Exon 2 of 7	ENSP00000389351.1	A0A0C4DG17
RPSA	ENST00000475346.1	TSL:1	n.73T>C	non_coding_transcript_exon	Exon 2 of 2

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

GnomAD2 exomes

AF:

0.460

AC:

107557

AN:

233646

AF XY:

0.460

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 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

African (AFR)

AF:

0.529

AC:

17548

AN:

33144

American (AMR)

AF:

0.431

AC:

19253

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

14617

AN:

26014

East Asian (EAS)

AF:

0.334

AC:

13242

AN:

39610

South Asian (SAS)

AF:

0.376

AC:

32271

AN:

85906

European-Finnish (FIN)

AF:

0.438

AC:

16654

AN:

37994

Middle Eastern (MID)

AF:

0.451

AC:

2444

AN:

5420

European-Non Finnish (NFE)

AF:

0.505

AC:

554202

AN:

1096528

Other (OTH)

AF:

0.490

AC:

29241

AN:

59692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.427

Heterozygous variant carriers

15828

31655

47483

63310

79138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15852

31704

47556

63408

79260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.496

AC:

75360

AN:

152044

Hom.:

19015

Cov.:

AF XY:

0.489

AC XY:

36346

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.533

AC:

22114

AN:

41456

American (AMR)

AF:

0.469

AC:

7166

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.560

AC:

1941

AN:

3466

East Asian (EAS)

AF:

0.330

AC:

1707

AN:

5170

South Asian (SAS)

AF:

0.382

AC:

1843

AN:

4822

European-Finnish (FIN)

AF:

0.429

AC:

4524

AN:

10550

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.508

AC:

34529

AN:

67990

Other (OTH)

AF:

0.490

AC:

1034

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1955

3910

5864

7819

9774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.506

Hom.:

7905

Bravo

AF:

0.498

Asia WGS

AF:

0.365

AC:

1274

AN:

3478

EpiCase

AF:

0.503

EpiControl

AF:

0.512

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial isolated congenital asplenia (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

1.3

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over