Genetic Variant MRPL51:c.190+48G>C (chr12-6492814-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016497.4(MRPL51):c.190+48G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,520,864 control chromosomes in the GnomAD database, including 68,492 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 0.35 ( 10343 hom., cov: 32)

Exomes 𝑓: 0.29 ( 58149 hom. )

Consequence

MRPL51
NM_016497.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.74

Publications

18 publications found

Variant links:

Genes affected

MRPL51 (HGNC:14044): (mitochondrial ribosomal protein L51) 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. Pseudogenes corresponding to this gene are found on chromosomes 4p and 21q. [provided by RefSeq, Jul 2008]

MRPL51 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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL51	NM_016497.4 link	c.190+48G>C		intron_variant	Intron 2 of 2	ENST00000229238.5	NP_057581.2	Q4U2R6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL51	ENST00000229238.5 link	c.190+48G>C		intron_variant	Intron 2 of 2	1	NM_016497.4	ENSP00000229238.3		Q4U2R6

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53641

AN:

151812

Hom.:

10330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.516

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.433

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.416

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.374

GnomAD2 exomes

AF:

0.316

AC:

78865

AN:

249690

AF XY:

0.309

show subpopulations

Gnomad AFR exome

AF:

0.521

Gnomad AMR exome

AF:

0.414

Gnomad ASJ exome

AF:

0.423

Gnomad EAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.256

Gnomad NFE exome

AF:

0.287

Gnomad OTH exome

AF:

0.324

GnomAD4 exome

AF:

0.285

AC:

390712

AN:

1368934

Hom.:

58149

Cov.:

AF XY:

0.285

AC XY:

195375

AN XY:

685604

show subpopulations

African (AFR)

AF:

0.531

AC:

16609

AN:

31286

American (AMR)

AF:

0.410

AC:

18269

AN:

44518

Ashkenazi Jewish (ASJ)

AF:

0.429

AC:

10980

AN:

25598

East Asian (EAS)

AF:

0.215

AC:

8445

AN:

39246

South Asian (SAS)

AF:

0.264

AC:

22236

AN:

84302

European-Finnish (FIN)

AF:

0.261

AC:

13899

AN:

53308

Middle Eastern (MID)

AF:

0.411

AC:

2304

AN:

5606

European-Non Finnish (NFE)

AF:

0.273

AC:

280305

AN:

1027814

Other (OTH)

AF:

0.309

AC:

17665

AN:

57256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

14719

29439

44158

58878

73597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9140

18280

27420

36560

45700

<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:

0.353

AC:

53696

AN:

151930

Hom.:

10343

Cov.:

AF XY:

0.351

AC XY:

26086

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.515

AC:

21328

AN:

41388

American (AMR)

AF:

0.361

AC:

5506

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

1500

AN:

3468

East Asian (EAS)

AF:

0.222

AC:

1152

AN:

5178

South Asian (SAS)

AF:

0.266

AC:

1284

AN:

4828

European-Finnish (FIN)

AF:

0.258

AC:

2723

AN:

10546

Middle Eastern (MID)

AF:

0.399

AC:

115

AN:

288

European-Non Finnish (NFE)

AF:

0.280

AC:

19057

AN:

67958

Other (OTH)

AF:

0.370

AC:

781

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1681

3362

5044

6725

8406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.256

Hom.:

947

Bravo

AF:

0.372

Asia WGS

AF:

0.284

AC:

989

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.14

(source)

DANN

Benign

0.32

PhyloP100

-3.7

PromoterAI

0.0089

Neutral

(source)

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over