chr18-49490920-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001199356.2(RPL17-C18orf32):c.-26G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

RPL17-C18orf32
NM_001199356.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.81

Variant links:

Genes affected

RPL17 (HGNC:10307): (ribosomal protein L17) 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 60S subunit. The protein belongs to the L22P family of ribosomal proteins. It is located in the cytoplasm. This gene has been referred to as rpL23 because the encoded protein shares amino acid identity with ribosomal protein L23 from Halobacterium marismortui; however, its official symbol is RPL17. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream C18orf32 (chromosome 18 open reading frame 32) gene. [provided by RefSeq, Dec 2010]

RPL17 links:

RPL17-C18orf32 (HGNC:44661): (RPL17-C18orf32 readthrough) This locus represents naturally occurring read-through transcription between the neighboring RPL17 (ribosomal protein L17) and C18orf32 (chromosome 18 open reading frame 32) genes. Alternative splicing results in multiple transcript variants. The encoded isoforms share sequence identity with the RPL17 protein, but they include frameshifted C-terminal regions derived from the downstream gene exons. [provided by RefSeq, Dec 2010]

RPL17-C18orf32 links:

ENSG00000265496 (HGNC:):

ENSG00000265496 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL17	NM_001035006.5 link	c.89G>A	p.Arg30His	missense_variant	Exon 4 of 7	ENST00000580261.6	NP_001030178.1	P18621-1A0A024R261

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL17	ENST00000580261.6 link	c.89G>A	p.Arg30His	missense_variant	Exon 4 of 7	1	NM_001035006.5	ENSP00000462385.1		P18621-1
RPL17-C18orf32	ENST00000584895.5 link	c.89G>A	p.Arg30His	missense_variant	Exon 3 of 7	3		ENSP00000463379.1		A0A0A6YYL6

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248768

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135036

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461614

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.89G>A (p.R30H) alteration is located in exon 4 (coding exon 3) of the RPL17 gene. This alteration results from a G to A substitution at nucleotide position 89, causing the arginine (R) at amino acid position 30 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;T;T;T;T;T;.;.;.;.;.;.;.;.;.

Eigen

Benign

0.060

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.83

T;.;.;.;.;T;T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.59

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.2

.;M;M;M;M;M;.;.;.;.;.;.;.;.;.

Sift4G

Benign

0.074

T;T;T;T;T;T;T;T;T;T;T;.;.;.;T

Polyphen

0.0030

.;B;B;B;B;B;.;.;.;.;.;.;.;.;.

Vest4

0.85

MutPred

0.71

Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);.;Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);

MVP

0.42

MPC

1.3

ClinPred

0.59

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over