Genetic Variant NM_016093.4:c.167A>G (chr5-172960040-A-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_016093.4(RPL26L1):c.167A>G(p.Gln56Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000116 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. 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. Q56P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

RPL26L1
NM_016093.4 missense, splice_region

Scores

Splicing: ADA: 0.9818

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.04

Publications

0 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:

RPL26L1-AS1 (HGNC:55914): (RPL26L1 antisense RNA 1)

RPL26L1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

BS2

High AC in GnomAdExome4 at 17 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.167A>G	p.Gln56Arg	missense splice_region	Exon 2 of 4	NP_057177.1	Q9UNX3
RPL26L1	NM_001317980.2		c.167A>G	p.Gln56Arg	missense splice_region	Exon 2 of 4	NP_001304909.1	Q9UNX3
RPL26L1	NM_001317981.2		c.167A>G	p.Gln56Arg	missense splice_region	Exon 2 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.167A>G	p.Gln56Arg	missense splice_region	Exon 2 of 4	ENSP00000265100.2	Q9UNX3
RPL26L1	ENST00000519156.1	TSL:1	c.167A>G	p.Gln56Arg	missense splice_region	Exon 1 of 3	ENSP00000430673.1	E5RIT6
RPL26L1	ENST00000519239.5	TSL:2	c.167A>G	p.Gln56Arg	missense splice_region	Exon 2 of 4	ENSP00000430147.1	Q9UNX3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000598

AC:

AN:

251026

AF XY:

0.0000516

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000434

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:

0.0000116

AC:

AN:

1461766

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.000358

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111958

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000576

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.060

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.058

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0056

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

PhyloP100

7.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.5

REVEL

Benign

0.24

Sift

Benign

0.23

Sift4G

Benign

0.53

Polyphen

0.0

Vest4

0.77

MutPred

0.35

Gain of MoRF binding (P = 0.0415)

MVP

0.40

MPC

0.77

ClinPred

0.17

GERP RS

4.9

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.30

gMVP

0.60

Mutation Taster

=50/50

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.87

SpliceAI score (max)

0.16

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