NM_053050.5:c.10G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

46 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053050.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MRPL53	NM_053050.5	MANE Select	c.10G>T	p.Ala4Ser	missense	Exon 1 of 3	NP_444278.1
CCDC142	NM_001365575.2	MANE Select	c.*1895G>T		downstream_gene	N/A	NP_001352504.1
CCDC142	NM_032779.4		c.*1895G>T		downstream_gene	N/A	NP_116168.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MRPL53	ENST00000258105.8	TSL:1 MANE Select	c.10G>T	p.Ala4Ser	missense	Exon 1 of 3	ENSP00000258105.7
MRPL53	ENST00000409710.1	TSL:2	c.10G>T	p.Ala4Ser	missense	Exon 1 of 2	ENSP00000386920.1
CCDC142	ENST00000454193.5	TSL:2	n.*144G>T		non_coding_transcript_exon	Exon 9 of 11	ENSP00000415532.1

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

GnomAD2 exomes

AF:

0.260

AC:

65408

AN:

251248

AF XY:

0.247

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 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

African (AFR)

AF:

0.736

AC:

24650

AN:

33476

American (AMR)

AF:

0.259

AC:

11568

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

3295

AN:

26136

East Asian (EAS)

AF:

0.833

AC:

33080

AN:

39698

South Asian (SAS)

AF:

0.271

AC:

23375

AN:

86248

European-Finnish (FIN)

AF:

0.140

AC:

7459

AN:

53418

Middle Eastern (MID)

AF:

0.182

AC:

1048

AN:

5768

European-Non Finnish (NFE)

AF:

0.135

AC:

150077

AN:

1111904

Other (OTH)

AF:

0.228

AC:

13754

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

10233

20466

30698

40931

51164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6010

12020

18030

24040

30050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.337

AC:

51366

AN:

152196

Hom.:

14160

Cov.:

AF XY:

0.337

AC XY:

25109

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.717

AC:

29758

AN:

41500

American (AMR)

AF:

0.266

AC:

4068

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

429

AN:

3472

East Asian (EAS)

AF:

0.824

AC:

4261

AN:

5174

South Asian (SAS)

AF:

0.300

AC:

1446

AN:

4826

European-Finnish (FIN)

AF:

0.137

AC:

1456

AN:

10602

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.133

AC:

9062

AN:

68000

Other (OTH)

AF:

0.291

AC:

616

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1242

2484

3727

4969

6211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.212

Hom.:

15277

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.9

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.0055

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0000010

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.21

PhyloP100

0.41

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.28

REVEL

Benign

0.049

Sift

Benign

0.75

Sift4G

Benign

0.58

Polyphen

0.0

Vest4

0.10

MPC

0.42

ClinPred

0.0040

GERP RS

2.3

PromoterAI

0.074

Neutral

(source)

Varity_R

0.040

gMVP

0.19

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over