18-49490871-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001035006.5(RPL17):c.138G>T(p.Lys46Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,462 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: 0.0000021 ( 0 hom. )

Consequence

RPL17
NM_001035006.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.992

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26435888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL17	NM_001035006.5 link	c.138G>T	p.Lys46Asn	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.138G>T	p.Lys46Asn	missense_variant	Exon 4 of 7	1	NM_001035006.5	ENSP00000462385.1		P18621-1
RPL17-C18orf32	ENST00000584895.5 link	c.138G>T	p.Lys46Asn	missense_variant	Exon 3 of 7	3		ENSP00000463379.1		A0A0A6YYL6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249344

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135276

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461462

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727012

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.138G>T (p.K46N) alteration is located in exon 4 (coding exon 3) of the RPL17 gene. This alteration results from a G to T substitution at nucleotide position 138, causing the lysine (K) at amino acid position 46 to be replaced by an asparagine (N). 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

0.84

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

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

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.061

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

D;D;.;.;.;.;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.26

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.64

.;.;N;N;N;N;.;N;.;.;.;.;.;.;.;.;.

PROVEAN

Benign

-2.2

.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.071

Sift

Uncertain

0.0090

.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Sift4G

Uncertain

0.053

T;D;T;T;T;T;T;T;T;T;T;T;T;.;.;.;D

Polyphen

0.075

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

Vest4

0.73

MutPred

0.48

Loss of phosphorylation at T45 (P = 0.0837);.;Loss of phosphorylation at T45 (P = 0.0837);Loss of phosphorylation at T45 (P = 0.0837);Loss of phosphorylation at T45 (P = 0.0837);Loss of phosphorylation at T45 (P = 0.0837);.;Loss of phosphorylation at T45 (P = 0.0837);.;Loss of phosphorylation at T45 (P = 0.0837);Loss of phosphorylation at T45 (P = 0.0837);Loss of phosphorylation at T45 (P = 0.0837);Loss of phosphorylation at T45 (P = 0.0837);Loss of phosphorylation at T45 (P = 0.0837);Loss of phosphorylation at T45 (P = 0.0837);Loss of phosphorylation at T45 (P = 0.0837);Loss of phosphorylation at T45 (P = 0.0837);

MVP

0.51

MPC

2.2

ClinPred

0.78

GERP RS

1.8

Varity_R

0.21

gMVP

0.62

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

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