3-23917997-T-G

Position:

chr3-23917997-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000307839.10(RPL15):c.138T>G(p.Asp46Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000869 in 1,610,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

RPL15
ENST00000307839.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.126

Variant links:

Genes affected

RPL15 (HGNC:10306): (ribosomal protein L15) 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 L15E family of ribosomal proteins and a component of the 60S subunit. This gene shares sequence similarity with the yeast ribosomal protein YL10 gene. Elevated expression of this gene has been observed in esophageal tumors and gastric cancer tissues, and deletion of this gene has been observed in a Diamond-Blackfan anemia (DBA) patient. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Mar 2017]

RPL15 links:

RPL15 (HGNC:):

RPL15 links:

NKIRAS1 (HGNC:17899): (NFKB inhibitor interacting Ras like 1) Predicted to enable GTPase activating protein binding activity. Predicted to be involved in I-kappaB kinase/NF-kappaB signaling. Predicted to act upstream of or within several processes, including Ral protein signal transduction; lung alveolus development; and surfactant homeostasis. Located in cytosol and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

NKIRAS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL15	NM_002948.5 linkuse as main transcript	c.138T>G	p.Asp46Glu	missense_variant	2/4	ENST00000307839.10	NP_002939.2	P61313-1A0A024R2Q4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL15	ENST00000307839.10 linkuse as main transcript	c.138T>G	p.Asp46Glu	missense_variant	2/4	1	NM_002948.5	ENSP00000309334.5		P61313-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152180

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247222

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134090

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:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000823

AC:

AN:

1458708

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725802

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 26, 2023

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 2171701). This variant has not been reported in the literature in individuals affected with RPL15-related conditions. This variant is present in population databases (rs778175191, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 46 of the RPL15 protein (p.Asp46Glu). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.48

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

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.94

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

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.46

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

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.5

L;.;L;.;L;L;.;L;.;L;L;.;L

MutationTaster

Benign

1.0

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

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.1

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

REVEL

Uncertain

0.32

Sift

Benign

0.12

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

Sift4G

Benign

0.17

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

Polyphen

0.0060

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

Vest4

0.66

MutPred

0.80

Gain of glycosylation at P45 (P = 0.1466);Gain of glycosylation at P45 (P = 0.1466);Gain of glycosylation at P45 (P = 0.1466);Gain of glycosylation at P45 (P = 0.1466);Gain of glycosylation at P45 (P = 0.1466);Gain of glycosylation at P45 (P = 0.1466);Gain of glycosylation at P45 (P = 0.1466);Gain of glycosylation at P45 (P = 0.1466);Gain of glycosylation at P45 (P = 0.1466);Gain of glycosylation at P45 (P = 0.1466);Gain of glycosylation at P45 (P = 0.1466);Gain of glycosylation at P45 (P = 0.1466);Gain of glycosylation at P45 (P = 0.1466);

MVP

0.84

MPC

1.5

ClinPred

0.29

GERP RS

-3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.91

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

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