dbSNP rs932068728: RPL26:p.Arg126Leu (chr17-8377625-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_000987.5(RPL26):c.377G>T(p.Arg126Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,810 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RPL26
NM_000987.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.06

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.377G>T	p.Arg126Leu	missense_variant	Exon 4 of 4	ENST00000648839.1	NP_000978.1	P61254
RPL26	NM_001315530.2 link	c.377G>T	p.Arg126Leu	missense_variant	Exon 4 of 4		NP_001302459.1	P61254
RPL26	NM_001315531.2 link	c.377G>T	p.Arg126Leu	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.377G>T	p.Arg126Leu	missense_variant	Exon 4 of 4		NM_000987.5	ENSP00000498177.1		P61254
ENSG00000263809	ENST00000582471.1 link	n.310-1521G>T		intron_variant	Intron 3 of 5	5		ENSP00000463847.1		J3QQQ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724982

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;T;T;T;T

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.75

.;.;.;.;T

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.49

T;T;T;T;T

MetaSVM

Benign

-0.34

MutationAssessor

Pathogenic

3.2

M;M;M;M;M

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-4.2

.;D;.;.;.

REVEL

Uncertain

0.50

Sift

Uncertain

0.029

.;D;.;.;.

Sift4G

Uncertain

0.054

.;T;T;T;T

Polyphen

0.0020

B;B;B;B;B

Vest4

0.66, 0.66, 0.63, 0.68

MutPred

0.29

Loss of methylation at K130 (P = 0.0322);Loss of methylation at K130 (P = 0.0322);Loss of methylation at K130 (P = 0.0322);Loss of methylation at K130 (P = 0.0322);Loss of methylation at K130 (P = 0.0322);

MVP

0.60

MPC

1.2

ClinPred

0.99

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

gMVP

0.71

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over