NM_001013.4:c.484C>T

Variant names:

• chr19-54207474-C-T
• rs1325824131
• NM_001013.4:c.484C>T

Variant summary

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

The NM_001013.4(RPS9):​c.484C>T​(p.Arg162Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,298 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RPS9 NM_001013.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.53
• Publications: 0 publications found

Genes affected

RPS9 (HGNC:10442): (ribosomal protein S9) 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 S4P family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, multiple processed pseudogenes derived from this gene are dispersed through the genome. [provided by RefSeq, Jul 2008]

ENSG00000300077 (HGNC:):

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS9	NM_001013.4	MANE Select	c.484C>T	p.Arg162Cys	missense	Exon 5 of 5	NP_001004.2
	RPS9	NM_001321701.2		c.484C>T	p.Arg162Cys	missense	Exon 5 of 5	NP_001308630.1	P46781
	RPS9	NM_001321702.2		c.484C>T	p.Arg162Cys	missense	Exon 5 of 5	NP_001308631.1	P46781

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS9	ENST00000302907.9	TSL:1 MANE Select	c.484C>T	p.Arg162Cys	missense	Exon 5 of 5	ENSP00000302896.4	P46781
	RPS9	ENST00000391753.6	TSL:1	c.484C>T	p.Arg162Cys	missense	Exon 4 of 4	ENSP00000375633.2	P46781
	RPS9	ENST00000441429.1	TSL:1	c.*948C>T		3_prime_UTR	Exon 3 of 3	ENSP00000414314.1	C9JM19

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461298 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726928

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5352

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60338

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000993999), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.5
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.17
Sift	Benign	0.095	T
Sift4G	Benign	0.063	T
Polyphen		0.92	P
Vest4		0.70
MutPred		0.39		Loss of MoRF binding (P = 6e-04)
MVP		0.57
MPC		2.6
ClinPred		0.86	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.59
gMVP		0.82
Mutation Taster		=89/11	polymorphism

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

dbSNP: rs1325824131; hg19: chr19-54711342;