chr17-8377644-C-T

Variant names:

Variant summary

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

The NM_000987.5(RPL26):c.358G>A(p.Glu120Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E120G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPL26
NM_000987.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.78

Variant links:

Genes affected

RPL26 (HGNC:10327): (ribosomal protein L26) 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 L24P family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Mutations in this gene result in Diamond-Blackfan anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

RPL26 links:

ENSG00000263809 (HGNC:):

ENSG00000263809 links:

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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
RPL26	NM_000987.5 link	c.358G>A	p.Glu120Lys	missense_variant	Exon 4 of 4	ENST00000648839.1	NP_000978.1	P61254
RPL26	NM_001315530.2 link	c.358G>A	p.Glu120Lys	missense_variant	Exon 4 of 4		NP_001302459.1	P61254
RPL26	NM_001315531.2 link	c.358G>A	p.Glu120Lys	missense_variant	Exon 4 of 4		NP_001302460.1	P61254

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL26	ENST00000648839.1 link	c.358G>A	p.Glu120Lys	missense_variant	Exon 4 of 4		NM_000987.5	ENSP00000498177.1		P61254
ENSG00000263809	ENST00000582471.1 link	n.310-1540G>A		intron_variant	Intron 3 of 5	5		ENSP00000463847.1		J3QQQ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248790

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459054

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725978

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Diamond-Blackfan anemia

Uncertain:1

Jul 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 120 of the RPL26 protein (p.Glu120Lys). This variant is present in population databases (rs757117420, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with RPL26-related conditions. 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. 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;T;T;T;T

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

.;.;.;.;D

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.47

T;T;T;T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.7

L;L;L;L;L

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.3

.;D;.;.;.

REVEL

Uncertain

0.58

Sift

Uncertain

0.029

.;D;.;.;.

Sift4G

Benign

0.082

.;T;T;T;T

Polyphen

0.011

B;B;B;B;B

Vest4

0.80, 0.80, 0.79, 0.81

MutPred

0.52

Gain of methylation at E120 (P = 0.0177);Gain of methylation at E120 (P = 0.0177);Gain of methylation at E120 (P = 0.0177);Gain of methylation at E120 (P = 0.0177);Gain of methylation at E120 (P = 0.0177);

MVP

0.77

MPC

1.6

ClinPred

0.92

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.66

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