Variant 8-144789826-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001317782.2(RPL8):c.752C>A(p.Thr251Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,613,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

RPL8
NM_001317782.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.72

Variant links:

Genes affected

RPL8 (HGNC:10368): (ribosomal protein L8) 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 L2P family of ribosomal proteins. It is located in the cytoplasm. In rat, the protein associates with the 5.8S rRNA, very likely participates in the binding of aminoacyl-tRNA, and is a constituent of the elongation factor 2-binding site at the ribosomal subunit interface. Alternatively spliced transcript variants encoding the same protein exist. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPL8 links:

RPL8 (HGNC:):

RPL8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2812613).

BS2

High AC in GnomAdExome4 at 38 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL8	NM_001317782.2 linkuse as main transcript	c.752C>A	p.Thr251Asn	missense_variant	5/5	ENST00000528957.6	NP_001304711.1	P62917
RPL8	NM_000973.5 linkuse as main transcript	c.752C>A	p.Thr251Asn	missense_variant	6/6		NP_000964.1	P62917
RPL8	NM_001317771.2 linkuse as main transcript	c.752C>A	p.Thr251Asn	missense_variant	6/6		NP_001304700.1	P62917
RPL8	NM_033301.3 linkuse as main transcript	c.752C>A	p.Thr251Asn	missense_variant	6/6		NP_150644.1	P62917

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL8	ENST00000528957.6 linkuse as main transcript	c.752C>A	p.Thr251Asn	missense_variant	5/5	1	NM_001317782.2	ENSP00000433464.2		P62917

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461186

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726896

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:

0.0000342

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.752C>A (p.T251N) alteration is located in exon 6 (coding exon 5) of the RPL8 gene. This alteration results from a C to A substitution at nucleotide position 752, causing the threonine (T) at amino acid position 251 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

T;T;T;T;.

Eigen

Benign

-0.025

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

.;D;.;D;D

M_CAP

Benign

0.0043

MetaRNN

Benign

0.28

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.;L;L;.

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.88

N;N;N;.;N

REVEL

Benign

0.10

Sift

Benign

0.16

T;T;T;.;T

Sift4G

Benign

0.20

T;T;T;T;.

Polyphen

0.0050

B;.;B;B;.

Vest4

0.61

MutPred

0.34

Loss of sheet (P = 0.0037);.;Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);.;

MVP

0.42

MPC

1.0

ClinPred

0.80

GERP RS

4.7

Varity_R

0.28

gMVP

0.81

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

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