Genetic Variant RPL31:p.Arg87Leu (chr2-101005985-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_000993.5(RPL31):c.260G>T(p.Arg87Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R87W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPL31
NM_000993.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.98

Publications

1 publications found

Variant links:

Genes affected

RPL31 (HGNC:10334): (ribosomal protein L31) 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 L31E family of ribosomal proteins. It is located in the cytoplasm. Higher levels of expression of this gene in familial adenomatous polyps compared to matched normal tissues have been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RPL31 links:

TBC1D8 (HGNC:17791): (TBC1 domain family member 8) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.817

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000993.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL31	NM_000993.5	MANE Select	c.260G>T	p.Arg87Leu	missense	Exon 4 of 5	NP_000984.1	P62899-1
RPL31	NM_001098577.3		c.260G>T	p.Arg87Leu	missense	Exon 4 of 5	NP_001092047.1	P62899-2
RPL31	NM_001099693.2		c.260G>T	p.Arg87Leu	missense	Exon 4 of 4	NP_001093163.1	P62899-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL31	ENST00000264258.8	TSL:1 MANE Select	c.260G>T	p.Arg87Leu	missense	Exon 4 of 5	ENSP00000264258.3	P62899-1
RPL31	ENST00000409733.5	TSL:1	c.260G>T	p.Arg87Leu	missense	Exon 3 of 4	ENSP00000386681.1	P62899-1
RPL31	ENST00000409320.7	TSL:1	c.260G>T	p.Arg87Leu	missense	Exon 4 of 4	ENSP00000387163.3	P62899-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460982

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726826

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5084

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111986

Other (OTH)

AF:

0.00

AC:

AN:

60328

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.73

M_CAP

Benign

0.074

MetaRNN

Pathogenic

0.82

MetaSVM

Uncertain

0.25

MutationAssessor

Uncertain

2.7

PhyloP100

8.0

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-5.6

REVEL

Uncertain

0.34

Sift

Uncertain

0.028

Sift4G

Uncertain

0.037

Polyphen

0.0050

Vest4

0.76

MutPred

0.58

Loss of catalytic residue at R87 (P = 0.0275)

MVP

0.79

MPC

1.4

ClinPred

0.99

GERP RS

3.3

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Varity_R

0.60

gMVP

0.88

Mutation Taster

=61/39

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over