Genetic Variant RPL26L1:p.Arg115Trp (chr5-172969446-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_016093.4(RPL26L1):c.343C>T(p.Arg115Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,244 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

RPL26L1
NM_016093.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

Publications

2 publications found

Variant links:

Genes affected

RPL26L1 (HGNC:17050): (ribosomal protein L26 like 1) This gene encodes a protein that shares high sequence similarity with ribosomal protein L26. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Dec 2015]

RPL26L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016093.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL26L1	NM_016093.4	MANE Select	c.343C>T	p.Arg115Trp	missense	Exon 4 of 4	NP_057177.1	Q9UNX3
RPL26L1	NM_001317980.2		c.343C>T	p.Arg115Trp	missense	Exon 4 of 4	NP_001304909.1	Q9UNX3
RPL26L1	NM_001317981.2		c.343C>T	p.Arg115Trp	missense	Exon 4 of 4	NP_001304910.1	Q9UNX3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL26L1	ENST00000265100.6	TSL:1 MANE Select	c.343C>T	p.Arg115Trp	missense	Exon 4 of 4	ENSP00000265100.2	Q9UNX3
RPL26L1	ENST00000519156.1	TSL:1	c.343C>T	p.Arg115Trp	missense	Exon 3 of 3	ENSP00000430673.1	E5RIT6
RPL26L1	ENST00000519239.5	TSL:2	c.343C>T	p.Arg115Trp	missense	Exon 4 of 4	ENSP00000430147.1	Q9UNX3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.000478

GnomAD2 exomes

AF:

0.0000478

AC:

AN:

251110

AF XY:

0.0000516

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000793

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461268

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726950

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33454

American (AMR)

AF:

0.0000895

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

1111602

Other (OTH)

AF:

0.0000828

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

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

AF:

0.0000329

AC:

AN:

151976

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41352

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67998

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

Eigen

Benign

-0.066

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.7

PhyloP100

1.6

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-7.7

REVEL

Benign

0.24

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.29

MutPred

0.62

Loss of disorder (P = 0.0066)

MVP

0.75

MPC

0.76

ClinPred

0.88

GERP RS

-1.1

Varity_R

0.83

gMVP

0.71

Mutation Taster

=71/29

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