4-151100479-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001006.5(RPS3A):​c.63-6A>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 0.00587 in 1,507,156 control chromosomes in the GnomAD database, including 363 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 0.028 ( 196 hom., cov: 33)
Exomes 𝑓: 0.0034 ( 167 hom. )

Consequence

RPS3A
NM_001006.5 splice_region, intron

Scores

2
Splicing: ADA: 0.00004188
2

Clinical Significance

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

Conservation

PhyloP100: 1.15
Variant links:
Genes affected
RPS3A (HGNC:10421): (ribosomal protein S3A) 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. The protein belongs to the S3AE family of ribosomal proteins. It is located in the cytoplasm. Disruption of the gene encoding rat ribosomal protein S3a, also named v-fos transformation effector protein, in v-fos-transformed rat cells results in reversion of the transformed phenotype. This gene is co-transcribed with the U73A and U73B small nucleolar RNA genes, which are located in its fourth and third introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 4-151100479-A-T is Benign according to our data. Variant chr4-151100479-A-T is described in ClinVar as [Benign]. Clinvar id is 778160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0946 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPS3ANM_001006.5 linkc.63-6A>T splice_region_variant, intron_variant Intron 1 of 5 ENST00000274065.9 NP_000997.1 P61247
RPS3ANM_001267699.2 linkc.63-6A>T splice_region_variant, intron_variant Intron 1 of 2 NP_001254628.1 B7Z3M5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPS3AENST00000274065.9 linkc.63-6A>T splice_region_variant, intron_variant Intron 1 of 5 1 NM_001006.5 ENSP00000346050.3 P61247

Frequencies

GnomAD3 genomes
AF:
0.0279
AC:
4242
AN:
152220
Hom.:
196
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0968
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00812
Gnomad ASJ
AF:
0.00605
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.000632
Gnomad OTH
AF:
0.0167
GnomAD2 exomes
AF:
0.00782
AC:
1958
AN:
250258
AF XY:
0.00589
show subpopulations
Gnomad AFR exome
AF:
0.0968
Gnomad AMR exome
AF:
0.00435
Gnomad ASJ exome
AF:
0.0134
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000617
Gnomad OTH exome
AF:
0.00394
GnomAD4 exome
AF:
0.00339
AC:
4588
AN:
1354818
Hom.:
167
Cov.:
20
AF XY:
0.00306
AC XY:
2083
AN XY:
680562
show subpopulations
Gnomad4 AFR exome
AF:
0.100
AC:
3120
AN:
31200
Gnomad4 AMR exome
AF:
0.00454
AC:
201
AN:
44298
Gnomad4 ASJ exome
AF:
0.0106
AC:
271
AN:
25452
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
39142
Gnomad4 SAS exome
AF:
0.000405
AC:
34
AN:
83888
Gnomad4 FIN exome
AF:
0.0000188
AC:
1
AN:
53282
Gnomad4 NFE exome
AF:
0.000441
AC:
448
AN:
1015100
Gnomad4 Remaining exome
AF:
0.00765
AC:
436
AN:
57012
Heterozygous variant carriers
0
205
411
616
822
1027
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
106
212
318
424
530
<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:
0.0280
AC:
4265
AN:
152338
Hom.:
196
Cov.:
33
AF XY:
0.0267
AC XY:
1986
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.0971
AC:
0.0970699
AN:
0.0970699
Gnomad4 AMR
AF:
0.00811
AC:
0.00810669
AN:
0.00810669
Gnomad4 ASJ
AF:
0.00605
AC:
0.00604839
AN:
0.00604839
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.000207
AC:
0.000206868
AN:
0.000206868
Gnomad4 FIN
AF:
0.00
AC:
0
AN:
0
Gnomad4 NFE
AF:
0.000632
AC:
0.000632093
AN:
0.000632093
Gnomad4 OTH
AF:
0.0166
AC:
0.016572
AN:
0.016572
Heterozygous variant carriers
0
199
399
598
798
997
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
46
92
138
184
230
<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:
0.00375
Hom.:
5
Bravo
AF:
0.0312
EpiCase
AF:
0.000819
EpiControl
AF:
0.00107

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Jun 13, 2018
Labcorp Genetics (formerly Invitae), Labcorp
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
-0.91
CADD
Benign
12
DANN
Benign
0.39
Mutation Taster
=75/25
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000042
dbscSNV1_RF
Benign
0.052
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs73859998; hg19: chr4-152021631; API