Genetic Variant NM_014175.4:c.59C>A (chr8-54135342-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014175.4(MRPL15):c.59C>A(p.Pro20Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000221 in 1,354,958 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

MRPL15
NM_014175.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67

Publications

0 publications found

Variant links:

Genes affected

MRPL15 (HGNC:14054): (mitochondrial ribosomal protein L15) 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 that belongs to the EcoL15 ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 15q. [provided by RefSeq, Jul 2008]

MRPL15 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014175.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL15	NM_014175.4	MANE Select	c.59C>A	p.Pro20Gln	missense	Exon 1 of 5	NP_054894.1	Q9P015

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPL15	ENST00000260102.9	TSL:1 MANE Select	c.59C>A	p.Pro20Gln	missense	Exon 1 of 5	ENSP00000260102.4	Q9P015
MRPL15	ENST00000867845.1		c.59C>A	p.Pro20Gln	missense	Exon 1 of 6	ENSP00000537904.1
MRPL15	ENST00000938846.1		c.59C>A	p.Pro20Gln	missense	Exon 1 of 5	ENSP00000608905.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000887

AC:

AN:

112696

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000221

AC:

AN:

1354958

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

668036

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28114

American (AMR)

AF:

0.00

AC:

AN:

30660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23314

East Asian (EAS)

AF:

0.0000324

AC:

AN:

30826

South Asian (SAS)

AF:

0.0000132

AC:

AN:

75760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5498

European-Non Finnish (NFE)

AF:

9.47e-7

AC:

AN:

1056500

Other (OTH)

AF:

0.00

AC:

AN:

55854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000101

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.091

MetaRNN

Uncertain

0.60

MetaSVM

Uncertain

0.12

MutationAssessor

Uncertain

2.8

PhyloP100

5.7

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-6.3

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.68

MutPred

0.15

Loss of methylation at R21 (P = 0.0554)

MVP

0.77

MPC

0.91

ClinPred

0.99

GERP RS

5.1

PromoterAI

0.038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.89

gMVP

0.73

Mutation Taster

=23/77

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over