dbSNP rs996955973: MRPL55:p.Ala21Thr (chr1-228108050-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181462.3(MRPL55):c.61G>A(p.Ala21Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,542,814 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

MRPL55
NM_181462.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.557

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042505622).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181462.3. 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.27-181G>A		intron	N/A	NP_852128.1	Q7Z7F7-1
MRPL55	NM_181462.3		c.61G>A	p.Ala21Thr	missense	Exon 4 of 6	NP_852127.2	Q7Z7F7-2
MRPL55	NM_001321284.2		c.27-181G>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.61G>A	p.Ala21Thr	missense	Exon 3 of 5	ENSP00000355699.1	Q7Z7F7-2
MRPL55	ENST00000336520.8	TSL:2 MANE Select	c.27-181G>A		intron	N/A	ENSP00000337342.3	Q7Z7F7-1
MRPL55	ENST00000366735.5	TSL:1	c.27-181G>A		intron	N/A	ENSP00000355696.1	Q7Z7F7-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD2 exomes

AF:

0.0000334

AC:

AN:

149846

AF XY:

0.0000377

show subpopulations

Gnomad AFR exome

AF:

0.000256

Gnomad AMR exome

AF:

0.0000417

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000348

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000180

AC:

AN:

1390482

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

684580

show subpopulations

African (AFR)

AF:

0.000128

AC:

AN:

31372

American (AMR)

AF:

0.0000856

AC:

AN:

35038

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24802

East Asian (EAS)

AF:

0.000309

AC:

AN:

35566

South Asian (SAS)

AF:

0.00

AC:

AN:

78692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

0.00000559

AC:

AN:

1073686

Other (OTH)

AF:

0.0000174

AC:

AN:

57544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

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:

0.0000197

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41574

American (AMR)

AF:

0.000131

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

0.10

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.5

(source)

DANN

Benign

0.79

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.27

M_CAP

Benign

0.0025

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.0

PhyloP100

-0.56

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.48

REVEL

Benign

0.010

Sift

Uncertain

0.011

Sift4G

Uncertain

0.030

Polyphen

0.0

Vest4

0.039

MutPred

0.20

Gain of phosphorylation at A21 (P = 0.0262)

MVP

0.076

ClinPred

0.0095

GERP RS

-1.6

PromoterAI

-0.062

Neutral

(source)

gMVP

0.069

Mutation Taster

=99/1

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over