Genetic Variant NM_180982.3:c.*564G>A (chr14-22834885-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_180982.3(MRPL52):c.*564G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,214 control chromosomes in the GnomAD database, including 3,193 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3190 hom., cov: 32)

Exomes 𝑓: 0.17 ( 3 hom. )

Consequence

MRPL52
NM_180982.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.708

Publications

28 publications found

Variant links:

Genes affected

MRPL52 (HGNC:16655): (mitochondrial ribosomal protein L52) 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 which has no bacterial homolog. Multiple transcript variants encoding different protein isoforms were identified through sequence analysis. [provided by RefSeq, Jul 2008]

MRPL52 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL52	NM_180982.3 link	c.*564G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000397496.7	NP_851313.1	Q86TS9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL52	ENST00000397496.7 link	c.*564G>A		3_prime_UTR_variant	Exon 5 of 5	2	NM_180982.3	ENSP00000380633.3		Q86TS9-3

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29142

AN:

151860

Hom.:

3186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.357

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.193

GnomAD4 exome

AF:

0.174

AC:

AN:

236

Hom.:

Cov.:

AF XY:

0.192

AC XY:

AN XY:

130

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.222

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

192

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.192

AC:

29170

AN:

151978

Hom.:

3190

Cov.:

AF XY:

0.193

AC XY:

14328

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.104

AC:

4311

AN:

41478

American (AMR)

AF:

0.157

AC:

2399

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

551

AN:

3466

East Asian (EAS)

AF:

0.359

AC:

1847

AN:

5152

South Asian (SAS)

AF:

0.224

AC:

1081

AN:

4820

European-Finnish (FIN)

AF:

0.238

AC:

2496

AN:

10506

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.232

AC:

15792

AN:

67972

Other (OTH)

AF:

0.199

AC:

420

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1198

2397

3595

4794

5992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.220

Hom.:

8477

Bravo

AF:

0.184

Asia WGS

AF:

0.310

AC:

1079

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.5

(source)

DANN

Benign

0.77

PhyloP100

0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over