chr2-101006060-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_000993.5(RPL31):c.335C>A(p.Thr112Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,613,312 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 2 hom. )

Consequence

RPL31
NM_000993.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 7.77

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.107972234).

BP6

Variant 2-101006060-C-A is Benign according to our data. Variant chr2-101006060-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2053046.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 177 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL31	NM_000993.5 link	c.335C>A	p.Thr112Asn	missense_variant	Exon 4 of 5	ENST00000264258.8	NP_000984.1	P62899-1
RPL31	NM_001098577.3 link	c.335C>A	p.Thr112Asn	missense_variant	Exon 4 of 5		NP_001092047.1	P62899-2
RPL31	NM_001099693.2 link	c.335C>A	p.Thr112Asn	missense_variant	Exon 4 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.335C>A	p.Thr112Asn	missense_variant	Exon 4 of 5	1	NM_000993.5	ENSP00000264258.3		P62899-1

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

177

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00207

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00103

AC:

257

AN:

250222

Hom.:

AF XY:

0.00105

AC XY:

142

AN XY:

135312

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00198

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00157

AC:

2289

AN:

1461018

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

1130

AN XY:

726788

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000561

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000282

Gnomad4 NFE exome

AF:

0.00193

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.00116

AC:

177

AN:

152294

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00207

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00172

Hom.:

Bravo

AF:

0.00120

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00110

AC:

133

EpiCase

AF:

0.00120

EpiControl

AF:

0.00196

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RPL31-related condition

Benign:1

Apr 16, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Jan 12, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

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

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

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

M_CAP

Benign

0.030

MetaRNN

Benign

0.11

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

MetaSVM

Uncertain

-0.029

MutationAssessor

Pathogenic

3.9

H;H;H;H;.;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.6

D;D;D;D;D;D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.028

D;D;D;D;D;D;D

Sift4G

Benign

0.061

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

Polyphen

0.036

B;.;.;B;P;P;.

Vest4

0.80

MVP

0.57

MPC

2.5

ClinPred

0.66

GERP RS

5.1

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.69

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over