6-132816991-T-G

Variant names:

• chr6-132816991-T-G
• NM_001016.4:c.266T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001016.4(RPS12):​c.266T>G​(p.Val89Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPS12 NM_001016.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.24
• Publications: 0 publications found

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]

SNORA33 (HGNC:32623): (small nucleolar RNA, H/ACA box 33)

SNORD100 (HGNC:32763): (small nucleolar RNA, C/D box 100)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS12	NM_001016.4	c.266T>G	p.Val89Gly	missense_variant	Exon 5 of 6	ENST00000230050.4	NP_001007.2
SNORA33	NR_002436.1	n.-228T>G		upstream_gene_variant
SNORD100	NR_002435.1	n.*114T>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS12	ENST00000230050.4	c.266T>G	p.Val89Gly	missense_variant	Exon 5 of 6	1	NM_001016.4	ENSP00000230050.3
RPS12	ENST00000484616.2	n.484T>G		non_coding_transcript_exon_variant	Exon 5 of 6	2
SNORA33	ENST00000363664.1	n.-228T>G		upstream_gene_variant		6
SNORD100	ENST00000408573.1	n.*114T>G		downstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.266T>G (p.V89G) alteration is located in exon 5 (coding exon 4) of the RPS12 gene. This alteration results from a T to G substitution at nucleotide position 266, causing the valine (V) at amino acid position 89 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	0.81
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.063
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.2
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.50	N
REVEL	Uncertain	0.34
Sift	Benign	0.11	T
Sift4G	Benign	0.13	T
Polyphen		0.0060	B
Vest4		0.67
MutPred		0.53		Loss of stability (P = 0.0664);
MVP		0.89
MPC		0.46
ClinPred		0.83	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.81
Mutation Taster		=30/70	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

Other links and lift over

hg19: chr6-133138130;