rs146810634

Variant names:

• chr1-153991137-C-A
• rs146810634
• NM_001030.6:c.29C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-153991137-C-A
• chr1-153991137-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_001030.6(RPS27):​c.29C>A​(p.Pro10His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,440,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P10L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: RPS27 NM_001030.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.71
• Publications: 4 publications found

Genes affected

RPS27 (HGNC:10416): (ribosomal protein S27) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the S27e family of ribosomal proteins and component of the 40S subunit. The encoded protein contains a C4-type zinc finger domain that can bind to zinc and may bind to nucleic acid. Mutations in this gene have been identified in numerous melanoma patients and in at least one patient with Diamond-Blackfan anemia (DBA). Elevated expression of this gene has been observed in various human cancers. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2018]

RPS27 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 17

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842
• BS2: High AC in GnomAdExome4 at 17 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030.6. 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
	RPS27	NM_001030.6	MANE Select	c.29C>A	p.Pro10His	missense	Exon 2 of 4	NP_001021.1	P42677
	RPS27	NM_001349946.2		c.-68C>A		5_prime_UTR	Exon 3 of 5	NP_001336875.1
	RPS27	NM_001349947.2		c.-68C>A		5_prime_UTR	Exon 2 of 4	NP_001336876.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS27	ENST00000651669.1	MANE Select	c.29C>A	p.Pro10His	missense	Exon 2 of 4	ENSP00000499044.1	P42677
	RPS27	ENST00000936806.1		c.152C>A	p.Pro51His	missense	Exon 3 of 5	ENSP00000606865.1
	RPS27	ENST00000936805.1		c.47C>A	p.Pro16His	missense	Exon 2 of 4	ENSP00000606864.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000443 AC: 1 AN: 225554 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.0000102

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000118 AC: 17 AN: 1440492 Hom.: 0 Cov.: 31 AF XY: 0.0000126 AC XY: 9 AN XY: 715326

African (AFR) AF: 0.00 AC: 0 AN: 32910

American (AMR) AF: 0.00 AC: 0 AN: 42318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25494

East Asian (EAS) AF: 0.00 AC: 0 AN: 39454

South Asian (SAS) AF: 0.00 AC: 0 AN: 84232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4390

European-Non Finnish (NFE) AF: 0.0000155 AC: 17 AN: 1100052

Other (OTH) AF: 0.00 AC: 0 AN: 59372

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000148 Hom.: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.31	T
PhyloP100		7.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-8.4	D
REVEL	Pathogenic	0.84
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.94
MutPred		0.42		Gain of solvent accessibility (P = 0.0055)
MVP		0.41
MPC		0.86
ClinPred		1.0	D
GERP RS		5.1
PromoterAI		-0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.90
gMVP		0.52
Mutation Taster		=61/39	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: rs146810634; hg19: chr1-153963613;