GeneBe

rs1064796859

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001011.4(RPS7):​c.-19+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RPS7
NM_001011.4 splice_donor, intron

Scores

2
Splicing: ADA: 0.9999
2

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 2.18

Publications

0 publications found
Variant links:
Genes affected
RPS7 (HGNC:10440): (ribosomal protein S7) 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 S7E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]
RPS7 Gene-Disease associations (from GenCC):
  • Diamond-Blackfan anemia 8
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
  • Diamond-Blackfan anemia
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 12 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-3575351-G-A is Pathogenic according to our data. Variant chr2-3575351-G-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 975849.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RPS7
NM_001011.4
MANE Select
c.-19+1G>A
splice_donor intron
N/ANP_001002.1P62081

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RPS7
ENST00000462576.5
TSL:1
c.-259G>A
5_prime_UTR
Exon 1 of 6ENSP00000495273.1P62081
RPS7
ENST00000645674.2
MANE Select
c.-19+1G>A
splice_donor intron
N/AENSP00000496757.1P62081
RPS7
ENST00000403564.5
TSL:2
c.-116G>A
5_prime_UTR
Exon 1 of 7ENSP00000385018.1P62081

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
0
GnomAD4 genome
Cov.:
33

ClinVar

ClinVar submissions
Significance:Likely pathogenic
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
2
-
-
Diamond-Blackfan anemia 8 (2)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
CADD
Pathogenic
28
DANN
Benign
0.87
PhyloP100
2.2
PromoterAI
-0.60
Under-expression
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Mutation Taster
=57/243
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.93
SpliceAI score (max)
1.0
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.75
Position offset: 3
DS_DL_spliceai
1.0
Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1064796859; hg19: chr2-3622941; API