Variant 8-80003129-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000276585.9(MRPS28):c.265C>T(p.Leu89Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00289 in 1,610,154 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.016 ( 60 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 50 hom. )

Consequence

MRPS28
ENST00000276585.9 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.34

Variant links:

Genes affected

MRPS28 (HGNC:14513): (mitochondrial ribosomal protein S28) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that has been called mitochondrial ribosomal protein S35 in the literature. [provided by RefSeq, Jul 2008]

MRPS28 links:

TPD52-MRPS28 (HGNC:):

TPD52-MRPS28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002919972).

BP6

Variant 8-80003129-G-A is Benign according to our data. Variant chr8-80003129-G-A is described in ClinVar as [Benign]. Clinvar id is 3037884.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS28	NM_014018.3 linkuse as main transcript	c.265C>T	p.Leu89Phe	missense_variant	2/3	ENST00000276585.9	NP_054737.1
TPD52-MRPS28	NM_001387778.1 linkuse as main transcript	c.487C>T	p.Leu163Phe	missense_variant	6/7		NP_001374707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS28	ENST00000276585.9 linkuse as main transcript	c.265C>T	p.Leu89Phe	missense_variant	2/3	1	NM_014018.3	ENSP00000276585	P1

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

2404

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0526

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0116

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:

0.000162

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00404

AC:

995

AN:

246406

Hom.:

AF XY:

0.00300

AC XY:

399

AN XY:

133090

show subpopulations

Gnomad AFR exome

AF:

0.0520

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000688

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00298

GnomAD4 exome

AF:

0.00155

AC:

2254

AN:

1457828

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

964

AN XY:

725102

show subpopulations

Gnomad4 AFR exome

AF:

0.0521

Gnomad4 AMR exome

AF:

0.00416

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000823

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000113

Gnomad4 OTH exome

AF:

0.00344

GnomAD4 genome

AF:

0.0158

AC:

2405

AN:

152326

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1136

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0525

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00271

Hom.:

Bravo

AF:

0.0179

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0504

AC:

222

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00464

AC:

564

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MRPS28-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 2019

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0048

T;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.77

N;N

REVEL

Benign

0.23

Sift

Benign

0.39

T;T

Sift4G

Benign

0.52

T;.

Polyphen

1.0

D;.

Vest4

0.60

MVP

0.76

MPC

0.60

ClinPred

0.036

GERP RS

5.1

Varity_R

0.11

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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