rs1192437249

Variant names:

• chr1-153991177-C-T
• rs1192437249
• NM_001030.6:c.69C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-153991177-C-T
• chr1-153991177-C-A
• chr1-153991177-C-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001030.6(RPS27):​c.69C>T​(p.Arg23Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,202 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPS27 NM_001030.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 1-153991177-C-T is Benign according to our data. Variant chr1-153991177-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2776912.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.11 with no splicing effect.

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.69C>T	p.Arg23Arg	synonymous	Exon 2 of 4	NP_001021.1	P42677
	RPS27	NM_001349946.2		c.-28C>T		5_prime_UTR	Exon 3 of 5	NP_001336875.1
	RPS27	NM_001349947.2		c.-28C>T		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.69C>T	p.Arg23Arg	synonymous	Exon 2 of 4	ENSP00000499044.1	P42677
	RPS27	ENST00000936804.1		c.190C>T	p.Pro64Ser	missense	Exon 3 of 5	ENSP00000606863.1
	RPS27	ENST00000936806.1		c.192C>T	p.Arg64Arg	synonymous	Exon 3 of 5	ENSP00000606865.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000861 AC: 2 AN: 232188 AF XY: 0.00000799

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000173

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000276 AC: 4 AN: 1447504 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718730

African (AFR) AF: 0.00 AC: 0 AN: 33248

American (AMR) AF: 0.0000229 AC: 1 AN: 43700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25700

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.00 AC: 0 AN: 84680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5252

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1103180

Other (OTH) AF: 0.00 AC: 0 AN: 59686

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

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	-0.26
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		-1.1
PromoterAI		-0.0051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs1192437249; hg19: chr1-153963653;