chr11-75401637-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001005.5(RPS3):c.162-3C>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 0.0115 in 1,597,172 control chromosomes in the GnomAD database, including 132 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 10 hom., cov: 33)

Exomes 𝑓: 0.012 ( 122 hom. )

Consequence

RPS3
NM_001005.5 splice_region, intron

Scores

Splicing: ADA: 0.0009152

Clinical Significance

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

Conservation

PhyloP100: 0.757

Publications

4 publications found

Variant links:

Genes affected

RPS3 (HGNC:10420): (ribosomal protein S3) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit, where it forms part of the domain where translation is initiated. The protein belongs to the S3P family of ribosomal proteins. Studies of the mouse and rat proteins have demonstrated that the protein has an extraribosomal role as an endonuclease involved in the repair of UV-induced DNA damage. The protein appears to be located in both the cytoplasm and nucleus but not in the nucleolus. Higher levels of expression of this gene in colon adenocarcinomas and adenomatous polyps compared to adjacent normal colonic mucosa have been observed. This gene is co-transcribed with the small nucleolar RNA genes U15A and U15B, which are located in its first and fifth introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

RPS3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 11-75401637-C-T is Benign according to our data. Variant chr11-75401637-C-T is described in ClinVar as Benign. ClinVar VariationId is 769802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1386 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS3	NM_001005.5	MANE Select	c.162-3C>T	splice_region intron	N/A	NP_000996.2
RPS3	NM_001260506.2		c.162-3C>T	splice_region intron	N/A	NP_001247435.1	P23396-2
RPS3	NM_001256802.2		c.162-3C>T	splice_region intron	N/A	NP_001243731.1	P23396-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS3	ENST00000531188.6	TSL:1 MANE Select	c.162-3C>T	splice_region intron	N/A	ENSP00000434643.1	P23396-1
RPS3	ENST00000524851.5	TSL:1	c.162-3C>T	splice_region intron	N/A	ENSP00000433821.1	P23396-1
RPS3	ENST00000530164.5	TSL:1	c.162-3C>T	splice_region intron	N/A	ENSP00000433155.1	F2Z2S8

Frequencies

GnomAD3 genomes

AF:

0.00911

AC:

1386

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00294

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0140

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00289

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00995

AC:

2501

AN:

251366

AF XY:

0.0103

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.0179

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.0145

Gnomad OTH exome

AF:

0.0147

GnomAD4 exome

AF:

0.0117

AC:

16975

AN:

1444838

Hom.:

122

Cov.:

AF XY:

0.0118

AC XY:

8503

AN XY:

719902

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

33178

American (AMR)

AF:

0.0139

AC:

623

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

426

AN:

26050

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39640

South Asian (SAS)

AF:

0.00230

AC:

198

AN:

85958

European-Finnish (FIN)

AF:

0.00114

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00925

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.0135

AC:

14834

AN:

1096374

Other (OTH)

AF:

0.0120

AC:

716

AN:

59830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

671

1343

2014

2686

3357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.00910

AC:

1386

AN:

152334

Hom.:

Cov.:

AF XY:

0.00854

AC XY:

636

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00293

AC:

122

AN:

41578

American (AMR)

AF:

0.0140

AC:

214

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0193

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00290

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0138

AC:

938

AN:

68040

Other (OTH)

AF:

0.0113

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

143

214

286

357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0141

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00092

dbscSNV1_RF

Benign

0.0040

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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