NM_001031.5:c.6C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001031.5(RPS28):​c.6C>G​(p.Asp2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D2D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

RPS28
NM_001031.5 missense

Scores

1
2
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.963
Variant links:
Genes affected
RPS28 (HGNC:10418): (ribosomal protein S28) 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 S28E 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]
NDUFA7 (HGNC:7691): (NADH:ubiquinone oxidoreductase subunit A7) This gene encodes a subunit of NADH:ubiquinone oxidoreductase (complex I), which is a multiprotein complex located in the inner mitochondrial membrane. Complex I functions in the transfer of electrons from NADH to the respiratory chain. [provided by RefSeq, Mar 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30618855).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPS28NM_001031.5 linkc.6C>G p.Asp2Glu missense_variant Exon 1 of 4 ENST00000600659.3 NP_001022.1 P62857B2R4R9
RPS28XM_047439201.1 linkc.6C>G p.Asp2Glu missense_variant Exon 1 of 3 XP_047295157.1
NDUFA7NM_005001.5 linkc.-178G>C upstream_gene_variant ENST00000301457.3 NP_004992.2 O95182
NDUFA7NR_135539.2 linkn.-161G>C upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPS28ENST00000600659.3 linkc.6C>G p.Asp2Glu missense_variant Exon 1 of 4 1 NM_001031.5 ENSP00000472469.1 P62857
NDUFA7ENST00000301457.3 linkc.-178G>C upstream_gene_variant 1 NM_005001.5 ENSP00000301457.1 O95182
ENSG00000167774ENST00000598884.1 linkn.-178G>C upstream_gene_variant 4 ENSP00000470609.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.97e-7
AC:
1
AN:
1435228
Hom.:
0
Cov.:
33
AF XY:
0.00000141
AC XY:
1
AN XY:
711602
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.08e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
1.2
DANN
Uncertain
0.99
DEOGEN2
Benign
0.23
T
Eigen
Benign
-0.94
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.62
T
M_CAP
Benign
0.079
D
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-0.96
T
PrimateAI
Pathogenic
0.82
D
Sift4G
Uncertain
0.044
D
Polyphen
0.23
B
Vest4
0.35
MutPred
0.69
Loss of MoRF binding (P = 0.1232);
MVP
0.34
MPC
1.6
ClinPred
0.76
D
GERP RS
-4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.079
gMVP
0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-8386420; API