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GeneBe

6-132814995-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001016.4(RPS12):c.38A>G(p.Asp13Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,612,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

RPS12
NM_001016.4 missense

Scores

7
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.23
Variant links:
Genes affected
RPS12 (HGNC:10385): (ribosomal protein S12) 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 S12E family of ribosomal proteins. It is located in the cytoplasm. Increased expression of this gene in colorectal cancers compared to matched normal colonic mucosa has been observed. 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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS12NM_001016.4 linkuse as main transcriptc.38A>G p.Asp13Gly missense_variant 3/6 ENST00000230050.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS12ENST00000230050.4 linkuse as main transcriptc.38A>G p.Asp13Gly missense_variant 3/61 NM_001016.4 P1
RPS12ENST00000484616.2 linkuse as main transcriptn.120A>G non_coding_transcript_exon_variant 3/62

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152136
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000876
AC:
22
AN:
251192
Hom.:
0
AF XY:
0.0000663
AC XY:
9
AN XY:
135746
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000185
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000168
AC:
246
AN:
1460628
Hom.:
0
Cov.:
30
AF XY:
0.000164
AC XY:
119
AN XY:
726740
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000150
Gnomad4 NFE exome
AF:
0.000205
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152254
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000638
Hom.:
0
Bravo
AF:
0.0000945
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 12, 2023The c.38A>G (p.D13G) alteration is located in exon 3 (coding exon 2) of the RPS12 gene. This alteration results from a A to G substitution at nucleotide position 38, causing the aspartic acid (D) at amino acid position 13 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.85
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.41
Cadd
Pathogenic
28
Dann
Uncertain
1.0
DEOGEN2
Benign
0.34
T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.036
D
MetaRNN
Uncertain
0.72
D
MetaSVM
Benign
-0.44
T
MutationAssessor
Pathogenic
3.0
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.91
D
PROVEAN
Pathogenic
-5.0
D
REVEL
Uncertain
0.49
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.042
D
Polyphen
0.22
B
Vest4
0.99
MVP
0.68
MPC
0.51
ClinPred
0.87
D
GERP RS
6.0
Varity_R
0.77
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs148631804; hg19: chr6-133136134; COSMIC: COSV105852645; COSMIC: COSV105852645; API