chr1-153991198-C-G

Variant names:

• chr1-153991198-C-G
• rs1649376584
• NM_001030.6:c.90C>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_001030.6(RPS27):​c.90C>G​(p.Ser30Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000691 in 1,446,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: RPS27 NM_001030.6 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.557
• Publications: 0 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=0.557 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 10 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.90C>G	p.Ser30Ser	synonymous	Exon 2 of 4	NP_001021.1	P42677
	RPS27	NM_001349946.2		c.-7C>G		5_prime_UTR	Exon 3 of 5	NP_001336875.1
	RPS27	NM_001349947.2		c.-7C>G		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.90C>G	p.Ser30Ser	synonymous	Exon 2 of 4	ENSP00000499044.1	P42677
	RPS27	ENST00000936804.1		c.211C>G	p.Leu71Val	missense	Exon 3 of 5	ENSP00000606863.1
	RPS27	ENST00000936806.1		c.213C>G	p.Ser71Ser	synonymous	Exon 3 of 5	ENSP00000606865.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000691 AC: 10 AN: 1446836 Hom.: 0 Cov.: 31 AF XY: 0.00000557 AC XY: 4 AN XY: 718342

African (AFR) AF: 0.0000301 AC: 1 AN: 33246

American (AMR) AF: 0.00 AC: 0 AN: 43652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25682

East Asian (EAS) AF: 0.00 AC: 0 AN: 39544

South Asian (SAS) AF: 0.00 AC: 0 AN: 84574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5584

European-Non Finnish (NFE) AF: 0.00000816 AC: 9 AN: 1102468

Other (OTH) AF: 0.00 AC: 0 AN: 59700

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		0.56
PromoterAI		0.058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs1649376584; hg19: chr1-153963674;