16-370060-G-C

Position:

chr16-370060-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006428.5(MRPL28):c.159C>G(p.Asn53Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,612,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

MRPL28
NM_006428.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05005768).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MRPL28	NM_006428.5 linkuse as main transcript	c.159C>G	p.Asn53Lys	missense_variant	2/6	ENST00000199706.13	NP_006419.2
MRPL28	XM_005255041.3 linkuse as main transcript	c.159C>G	p.Asn53Lys	missense_variant	2/6		XP_005255098.1
MRPL28	XM_011522351.3 linkuse as main transcript	c.159C>G	p.Asn53Lys	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.159C>G	p.Asn53Lys	missense_variant	2/6	1	NM_006428.5	ENSP00000199706	P1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000725

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000322

AC:

AN:

248274

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134814

show subpopulations

Gnomad AFR exome

AF:

0.000503

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1460692

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726638

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000197

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000722

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000215

ESP6500AA

AF:

0.000911

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000495

AC:

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

Aug 02, 2021

The c.159C>G (p.N53K) alteration is located in exon 2 (coding exon 1) of the MRPL28 gene. This alteration results from a C to G substitution at nucleotide position 159, causing the asparagine (N) at amino acid position 53 to be replaced by a lysine (K). 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

Pathogenic

0.64

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.064

T;T;T;T;T;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.73

.;.;T;T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.050

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.2

M;M;M;.;.;.

MutationTaster

Benign

0.78

N;N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.7

.;D;D;D;D;D

REVEL

Benign

0.095

Sift

Benign

0.11

.;T;T;T;T;T

Sift4G

Benign

0.38

.;T;T;.;.;.

Polyphen

0.035

B;B;B;B;.;.

Vest4

0.55

MutPred

0.34

Gain of methylation at N53 (P = 0.0221);Gain of methylation at N53 (P = 0.0221);Gain of methylation at N53 (P = 0.0221);Gain of methylation at N53 (P = 0.0221);Gain of methylation at N53 (P = 0.0221);Gain of methylation at N53 (P = 0.0221);

MVP

0.39

ClinPred

0.070

GERP RS

1.2

Varity_R

0.44

gMVP

0.72

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