Variant 12-6492309-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016497.4(MRPL51):c.349C>T(p.Leu117Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00133 in 1,612,866 control chromosomes in the GnomAD database, including 1 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 0.0010 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 0 hom. )

Consequence

MRPL51
NM_016497.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.74

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11631429).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL51	NM_016497.4 linkuse as main transcript	c.349C>T	p.Leu117Phe	missense_variant	3/3	ENST00000229238.5	NP_057581.2	Q4U2R6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL51	ENST00000229238.5 linkuse as main transcript	c.349C>T	p.Leu117Phe	missense_variant	3/3	1	NM_016497.4	ENSP00000229238.3		Q4U2R6

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

154

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00178

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000957

AC:

239

AN:

249858

Hom.:

AF XY:

0.000999

AC XY:

135

AN XY:

135082

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000968

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000660

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00169

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.00137

AC:

1997

AN:

1460502

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

979

AN XY:

726580

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.00104

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000814

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00165

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.00101

AC:

154

AN:

152364

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00178

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00143

Hom.:

Bravo

AF:

0.00117

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00108

AC:

131

EpiCase

AF:

0.00251

EpiControl

AF:

0.00160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Pathogenic

0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;T;T;.;T;T;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;.;.;D;.;D;D

M_CAP

Benign

0.075

MetaRNN

Benign

0.12

T;T;T;T;T;T;T

MetaSVM

Uncertain

0.046

MutationAssessor

Uncertain

2.8

M;.;.;.;.;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-4.0

D;.;.;.;.;.;.

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

D;.;.;.;.;.;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;.

Polyphen

1.0

D;.;.;.;.;.;.

Vest4

0.85

MVP

0.78

MPC

1.3

ClinPred

0.41

GERP RS

5.3

Varity_R

0.90

gMVP

0.92

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over