8-73292284-T-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_000971.4(RPL7):​c.245A>G​(p.Tyr82Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,612,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

RPL7
NM_000971.4 missense

Scores

6
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96

Publications

0 publications found
Variant links:
Genes affected
RPL7 (HGNC:10363): (ribosomal protein L7) 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 60S subunit. The protein belongs to the L30P family of ribosomal proteins. It contains an N-terminal basic region-leucine zipper (BZIP)-like domain and the RNP consensus submotif RNP2. In vitro the BZIP-like domain mediates homodimerization and stable binding to DNA and RNA, with a preference for 28S rRNA and mRNA. The protein can inhibit cell-free translation of mRNAs, suggesting that it plays a regulatory role in the translation apparatus. It is located in the cytoplasm. The protein has been shown to be an autoantigen in patients with systemic autoimmune diseases, such as systemic lupus erythematosus. 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.828
BS2
High AC in GnomAd4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000971.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RPL7
NM_000971.4
MANE Select
c.245A>Gp.Tyr82Cys
missense
Exon 3 of 7NP_000962.2
RPL7
NM_001363737.2
c.125A>Gp.Tyr42Cys
missense
Exon 3 of 7NP_001350666.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RPL7
ENST00000352983.7
TSL:1 MANE Select
c.245A>Gp.Tyr82Cys
missense
Exon 3 of 7ENSP00000339795.2
RPL7
ENST00000863689.1
c.245A>Gp.Tyr82Cys
missense
Exon 3 of 6ENSP00000533748.1
RPL7
ENST00000863690.1
c.245A>Gp.Tyr82Cys
missense
Exon 3 of 7ENSP00000533749.1

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
151938
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000199
AC:
5
AN:
250832
AF XY:
0.0000147
show subpopulations
Gnomad AFR exome
AF:
0.0000617
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000335
AC:
49
AN:
1460998
Hom.:
0
Cov.:
33
AF XY:
0.0000275
AC XY:
20
AN XY:
726858
show subpopulations
African (AFR)
AF:
0.0000598
AC:
2
AN:
33468
American (AMR)
AF:
0.0000224
AC:
1
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.0000504
AC:
2
AN:
39692
South Asian (SAS)
AF:
0.0000464
AC:
4
AN:
86252
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52852
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5740
European-Non Finnish (NFE)
AF:
0.0000360
AC:
40
AN:
1111768
Other (OTH)
AF:
0.00
AC:
0
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
4
8
11
15
19
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<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:
0.0000461
AC:
7
AN:
151938
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74200
show subpopulations
African (AFR)
AF:
0.0000484
AC:
2
AN:
41330
American (AMR)
AF:
0.00
AC:
0
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3464
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5180
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10564
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000735
AC:
5
AN:
67998
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.454
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000604
Hom.:
0
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.32
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.65
D
Eigen
Uncertain
0.20
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.033
D
MetaRNN
Pathogenic
0.83
D
MetaSVM
Benign
-0.58
T
MutationAssessor
Pathogenic
3.5
M
PhyloP100
5.0
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-8.3
D
REVEL
Uncertain
0.51
Sift
Uncertain
0.0080
D
Sift4G
Benign
0.068
T
Polyphen
0.17
B
Vest4
0.86
MutPred
0.67
Gain of catalytic residue at Y82 (P = 0.0486)
MVP
0.60
MPC
0.65
ClinPred
0.98
D
GERP RS
4.5
Varity_R
0.58
gMVP
0.90
Mutation Taster
=21/79
disease causing

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

Other links and lift over

dbSNP: rs748941975; hg19: chr8-74204519; COSMIC: COSV53584169; COSMIC: COSV53584169; API