Variant chr2-74472651-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_053050.5(MRPL53):c.10G>T(p.Ala4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,613,948 control chromosomes in the GnomAD database, including 55,147 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.34 ( 14160 hom., cov: 33)

Exomes 𝑓: 0.18 ( 40987 hom. )

Consequence

MRPL53
NM_053050.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.409

Variant links:

Genes affected

MRPL53 (HGNC:16684): (mitochondrial ribosomal protein L53) 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 pseudogene corresponding to this gene is found on chromosome 1p. [provided by RefSeq, Jul 2008]

MRPL53 links:

CCDC142 (HGNC:25889): (coiled-coil domain containing 142)

CCDC142 links:

ENSG00000286883 (HGNC:):

ENSG00000286883 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0074633E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL53	NM_053050.5 link	c.10G>T	p.Ala4Ser	missense_variant	1/3	ENST00000258105.8	NP_444278.1	Q96EL3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL53	ENST00000258105.8 link	c.10G>T	p.Ala4Ser	missense_variant	1/3	1	NM_053050.5	ENSP00000258105.7		Q96EL3

Frequencies

GnomAD3 genomes

AF:

0.337

AC:

51285

AN:

152078

Hom.:

14133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.823

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.291

GnomAD3 exomes

AF:

0.260

AC:

65408

AN:

251248

Hom.:

14759

AF XY:

0.247

AC XY:

33499

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.732

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.840

Gnomad SAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.135

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.204

GnomAD4 exome

AF:

0.184

AC:

268306

AN:

1461752

Hom.:

40987

Cov.:

AF XY:

0.184

AC XY:

133492

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.736

Gnomad4 AMR exome

AF:

0.259

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.833

Gnomad4 SAS exome

AF:

0.271

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.228

GnomAD4 genome

AF:

0.337

AC:

51366

AN:

152196

Hom.:

14160

Cov.:

AF XY:

0.337

AC XY:

25109

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.717

Gnomad4 AMR

AF:

0.266

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.824

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.291

Alfa

AF:

0.183

Hom.:

8223

Bravo

AF:

0.370

TwinsUK

AF:

0.139

AC:

514

ALSPAC

AF:

0.134

AC:

518

ESP6500AA

AF:

0.706

AC:

3112

ESP6500EA

AF:

0.138

AC:

1187

ExAC

AF:

0.268

AC:

32521

Asia WGS

AF:

0.566

AC:

1967

AN:

3478

EpiCase

AF:

0.138

EpiControl

AF:

0.142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.9

DANN

Benign

0.69

DEOGEN2

Benign

0.0055

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0000010

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.21

N;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.049

Sift

Benign

0.75

T;T

Sift4G

Benign

0.58

T;D

Polyphen

0.0

B;.

Vest4

0.10

MPC

0.42

ClinPred

0.0040

GERP RS

2.3

Varity_R

0.040

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over