Variant 16-370043-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_006428.5(MRPL28):c.176G>C(p.Arg59Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000397 in 1,613,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

MRPL28
NM_006428.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.95

Variant links:

Genes affected

MRPL28 (HGNC:14484): (mitochondrial ribosomal protein L28) 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 39S subunit protein, a part of which was originally isolated by its ability to recognize tyrosinase in an HLA-A24-restricted fashion. [provided by RefSeq, Jul 2008]

MRPL28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016733885).

BP6

Variant 16-370043-C-G is Benign according to our data. Variant chr16-370043-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 254105.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MRPL28	NM_006428.5 linkuse as main transcript	c.176G>C	p.Arg59Pro	missense_variant	2/6	ENST00000199706.13	NP_006419.2
MRPL28	XM_005255041.3 linkuse as main transcript	c.176G>C	p.Arg59Pro	missense_variant	2/6		XP_005255098.1
MRPL28	XM_011522351.3 linkuse as main transcript	c.176G>C	p.Arg59Pro	missense_variant	2/6		XP_011520653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL28	ENST00000199706.13 linkuse as main transcript	c.176G>C	p.Arg59Pro	missense_variant	2/6	1	NM_006428.5	ENSP00000199706	P1

Frequencies

GnomAD3 genomes

AF:

0.000454

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000514

AC:

128

AN:

249238

Hom.:

AF XY:

0.000540

AC XY:

AN XY:

135246

show subpopulations

Gnomad AFR exome

AF:

0.0000624

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000507

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000391

AC:

571

AN:

1460924

Hom.:

Cov.:

AF XY:

0.000409

AC XY:

297

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000359

Gnomad4 OTH exome

AF:

0.000845

GnomAD4 genome

AF:

0.000460

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000581

Hom.:

Bravo

AF:

0.000582

ExAC

AF:

0.000412

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.000831

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Oromandibular-limb hypogenesis spectrum

Benign:1

Likely benign, no assertion criteria provided

research

CHU Sainte-Justine Research Center, University of Montreal

Aug 12, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.015

T;T;T;T;T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.88

.;.;D;D;D;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.017

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;M;.;.;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.85

.;N;N;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.17

.;T;T;T;T;T

Sift4G

Benign

0.30

.;T;T;.;.;.

Polyphen

0.0080

B;B;B;B;.;.

Vest4

0.57

MVP

0.48

ClinPred

0.014

GERP RS

3.9

Varity_R

0.80

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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