17-8377650-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000987.5(RPL26):c.352A>G(p.Ile118Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I118F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RPL26
NM_000987.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.16

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia 11
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
Diamond-Blackfan anemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RPL26 links:

ENSG00000263809 (HGNC:):

ENSG00000263809 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27624884).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000987.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL26	NM_000987.5	MANE Select	c.352A>G	p.Ile118Val	missense	Exon 4 of 4	NP_000978.1	P61254
RPL26	NM_001315530.2		c.352A>G	p.Ile118Val	missense	Exon 4 of 4	NP_001302459.1	P61254
RPL26	NM_001315531.2		c.352A>G	p.Ile118Val	missense	Exon 4 of 4	NP_001302460.1	P61254

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL26	ENST00000648839.1	MANE Select	c.352A>G	p.Ile118Val	missense	Exon 4 of 4	ENSP00000498177.1	P61254
ENSG00000263809	ENST00000582471.1	TSL:5	n.310-1546A>G		intron	N/A	ENSP00000463847.1	J3QQQ9
RPL26	ENST00000913691.1		c.376A>G	p.Ile126Val	missense	Exon 4 of 4	ENSP00000583750.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249288

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000137

AC:

AN:

1459872

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.0000224

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111670

Other (OTH)

AF:

0.0000166

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.16

Eigen

Benign

0.080

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0078

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.3

PhyloP100

6.2

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.92

REVEL

Benign

0.20

Sift

Uncertain

0.021

Sift4G

Uncertain

0.059

Polyphen

0.0

Vest4

0.34

MutPred

0.51

Loss of methylation at K122 (P = 0.1073)

MVP

0.41

MPC

0.84

ClinPred

0.54

GERP RS

4.4

Varity_R

0.19

gMVP

0.35

Mutation Taster

=69/31

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over