Genetic Variant NM_000993.5:c.106G>T (chr2-101002807-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000993.5(RPL31):c.106G>T(p.Val36Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,320 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.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RPL31
NM_000993.5 missense, splice_region

Scores

Splicing: ADA: 0.9934

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.84

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL31	NM_000993.5 link	c.106G>T	p.Val36Leu	missense_variant, splice_region_variant	Exon 2 of 5	ENST00000264258.8	NP_000984.1	P62899-1
RPL31	NM_001098577.3 link	c.106G>T	p.Val36Leu	missense_variant, splice_region_variant	Exon 2 of 5		NP_001092047.1	P62899-2
RPL31	NM_001099693.2 link	c.106G>T	p.Val36Leu	missense_variant, splice_region_variant	Exon 2 of 4		NP_001093163.1	P62899-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL31	ENST00000264258.8 link	c.106G>T	p.Val36Leu	missense_variant, splice_region_variant	Exon 2 of 5	1	NM_000993.5	ENSP00000264258.3		P62899-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459320

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726172

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:

9.01e-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

0.76

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;T;.;.;T;T;.;.;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

.;.;D;D;D;D;D;D;D

M_CAP

Benign

0.0091

MetaRNN

Benign

0.33

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.4

M;.;M;M;M;.;.;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.0

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.047

D;D;T;D;D;T;D;D;D

Sift4G

Benign

0.083

T;T;T;T;T;T;T;T;T

Polyphen

0.0050

B;B;.;.;B;B;B;.;B

Vest4

0.50

MutPred

0.41

Loss of methylation at K40 (P = 0.1516);Loss of methylation at K40 (P = 0.1516);Loss of methylation at K40 (P = 0.1516);Loss of methylation at K40 (P = 0.1516);Loss of methylation at K40 (P = 0.1516);Loss of methylation at K40 (P = 0.1516);Loss of methylation at K40 (P = 0.1516);Loss of methylation at K40 (P = 0.1516);Loss of methylation at K40 (P = 0.1516);

MVP

0.59

MPC

1.2

ClinPred

0.83

GERP RS

5.4

Varity_R

0.18

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.81

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