1-153990790-C-T

Variant names:

• chr1-153990790-C-T
• rs181547215
• NM_001030.6:c.-7C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001030.6(RPS27):​c.-7C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000937 in 1,614,218 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0010 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00093 (2 hom.)
• Consequence: RPS27 NM_001030.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 2 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]

RAB13 (HGNC:9762): (RAB13, member RAS oncogene family) This gene is a member of the Rab family of small G proteins and plays a role in regulating membrane trafficking between trans-Golgi network (TGN) and recycling endosomes (RE). The encoded protein is involved in the assembly of tight junctions, which are components of the apical junctional complex (AJC) of epithelial cells. The AJC plays a role in forming a barrier between luminal contents and the underlying tissue. Additional functions associated with the protein include endocytic recycling of occludin, regulation of epithelial cell scattering, neuronal regeneration and regulation of neurite outgrowth. Alternately spliced transcript variants have been observed for this gene. A pseudogene associated with this gene is located on chromosome 12. [provided by RefSeq, Jan 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BS2: High AC in GnomAd4 at 152 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.-7C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_001021.1	P42677
	RPS27	NM_001030.6	MANE Select	c.-7C>T		5_prime_UTR	Exon 1 of 4	NP_001021.1	P42677
	RPS27	NM_001349946.2		c.-224C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001336875.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS27	ENST00000651669.1	MANE Select	c.-7C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000499044.1	P42677
	RPS27	ENST00000651669.1	MANE Select	c.-7C>T		5_prime_UTR	Exon 1 of 4	ENSP00000499044.1	P42677
	RPS27	ENST00000936806.1		c.-7C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000606865.1

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 153 AN: 152210 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00144 AC: 363 AN: 251486 AF XY: 0.00142

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00527

Gnomad FIN exome AF: 0.00115

Gnomad NFE exome AF: 0.00159

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000930 AC: 1360 AN: 1461890 Hom.: 2 Cov.: 31 AF XY: 0.000932 AC XY: 678 AN XY: 727248

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000268 AC: 12 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 30 AN: 26136

East Asian (EAS) AF: 0.00572 AC: 227 AN: 39700

South Asian (SAS) AF: 0.000580 AC: 50 AN: 86258

European-Finnish (FIN) AF: 0.00133 AC: 71 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000826 AC: 918 AN: 1112008

Other (OTH) AF: 0.000795 AC: 48 AN: 60396

GnomAD4 genome AF: 0.000998 AC: 152 AN: 152328 Hom.: 1 Cov.: 32 AF XY: 0.000940 AC XY: 70 AN XY: 74486

African (AFR) AF: 0.0000722 AC: 3 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5182

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4834

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00131 AC: 89 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00108 Hom.: 0

Bravo AF: 0.000892

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00125

EpiControl AF: 0.000948

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		1.6
PromoterAI		-0.15	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2
Mutation Taster		=298/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs181547215; hg19: chr1-153963266; COSMIC: COSV55144219; COSMIC: COSV55144219;