Genetic Variant ENST00000366738.5:c.52G>A (chr1-228108059-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000366738.5(MRPL55):c.52G>A(p.Gly18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000013 in 1,541,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

MRPL55
ENST00000366738.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.40

Publications

0 publications found

Variant links:

Genes affected

MRPL55 (HGNC:16686): (mitochondrial ribosomal protein L55) 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. Multiple transcript variants encoding two different isoforms were identified through sequence analysis. [provided by RefSeq, Jul 2008]

MRPL55 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037472874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000366738.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPL55	NM_181463.3	MANE Select	c.26+176G>A		intron	N/A	NP_852128.1	Q7Z7F7-1
MRPL55	NM_181462.3		c.52G>A	p.Gly18Ser	missense	Exon 4 of 6	NP_852127.2	Q7Z7F7-2
MRPL55	NM_001321284.2		c.26+176G>A		intron	N/A	NP_001308213.1	Q7Z7F7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPL55	ENST00000366738.5	TSL:1	c.52G>A	p.Gly18Ser	missense	Exon 3 of 5	ENSP00000355699.1	Q7Z7F7-2
MRPL55	ENST00000336520.8	TSL:2 MANE Select	c.26+176G>A		intron	N/A	ENSP00000337342.3	Q7Z7F7-1
MRPL55	ENST00000366735.5	TSL:1	c.26+176G>A		intron	N/A	ENSP00000355696.1	Q7Z7F7-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.20e-7

AC:

AN:

1388774

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31302

American (AMR)

AF:

0.00

AC:

AN:

34790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24702

East Asian (EAS)

AF:

0.00

AC:

AN:

35548

South Asian (SAS)

AF:

0.00

AC:

AN:

78562

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48124

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

9.32e-7

AC:

AN:

1072636

Other (OTH)

AF:

0.00

AC:

AN:

57460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

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

Benign

0.096

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.18

(source)

DANN

Benign

0.50

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.31

M_CAP

Benign

0.0019

MetaRNN

Benign

0.037

MetaSVM

Benign

-1.0

PhyloP100

-2.4

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.20

REVEL

Benign

0.0090

Sift

Benign

0.58

Sift4G

Benign

0.74

Polyphen

0.074

Vest4

0.12

MutPred

0.071

Gain of disorder (P = 0.0531)

MVP

0.061

ClinPred

0.035

GERP RS

-3.6

PromoterAI

0.024

Neutral

(source)

gMVP

0.062

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over