17-8377641-G-A

Position:

chr17-8377641-G-A

Variant summary

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

The NM_000987.5(RPL26):c.361C>T(p.Arg121Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,458,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

RPL26
NM_000987.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.54

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:

(HGNC:):

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 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RPL26	NM_000987.5 linkuse as main transcript	c.361C>T	p.Arg121Trp	missense_variant	4/4	ENST00000648839.1
RPL26	NM_001315530.2 linkuse as main transcript	c.361C>T	p.Arg121Trp	missense_variant	4/4
RPL26	NM_001315531.2 linkuse as main transcript	c.361C>T	p.Arg121Trp	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL26	ENST00000648839.1 linkuse as main transcript	c.361C>T	p.Arg121Trp	missense_variant	4/4		NM_000987.5	P1
	ENST00000666354.1 linkuse as main transcript	n.154-3404G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248430

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134584

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1458228

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725620

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

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

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Feb 18, 2021

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). This variant has not been reported in the literature in individuals with RPL26-related conditions. This variant is present in population databases (rs763691423, ExAC 0.006%). This sequence change replaces arginine with tryptophan at codon 121 of the RPL26 protein (p.Arg121Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Benign

0.92

DEOGEN2

Uncertain

0.59

D;D;D;D;D

Eigen

Benign

0.073

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.88

M_CAP

Benign

0.069

MetaRNN

Uncertain

0.53

D;D;D;D;D

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.5

M;M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.81

Polyphen

0.072

B;B;B;B;B

Vest4

0.59, 0.60, 0.56

MutPred

0.61

Gain of catalytic residue at L119 (P = 0.0081);Gain of catalytic residue at L119 (P = 0.0081);Gain of catalytic residue at L119 (P = 0.0081);Gain of catalytic residue at L119 (P = 0.0081);Gain of catalytic residue at L119 (P = 0.0081);

MVP

0.47

MPC

1.0

ClinPred

0.85

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

gMVP

0.72

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