6-43675226-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_018135.4(MRPS18A):c.422C>G(p.Pro141Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00189 in 1,521,632 control chromosomes in the GnomAD database, including 53 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P141L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.010 ( 36 hom., cov: 32)

Exomes 𝑓: 0.00095 ( 17 hom. )

Consequence

MRPS18A
NM_018135.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.34

Publications

1 publications found

Variant links:

Genes affected

MRPS18A (HGNC:14515): (mitochondrial ribosomal protein S18A) 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 28S subunit protein that belongs to the ribosomal protein S18P family. The encoded protein is one of three that has significant sequence similarity to bacterial S18 proteins. The primary sequences of the three human mitochondrial S18 proteins are no more closely related to each other than they are to the prokaryotic S18 proteins. A pseudogene corresponding to this gene is found on chromosome 3p. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jul 2010]

MRPS18A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006073177).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0103 (1570/152236) while in subpopulation AFR AF = 0.0357 (1483/41516). AF 95% confidence interval is 0.0342. There are 36 homozygotes in GnomAd4. There are 744 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 36 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018135.4. 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
	MRPS18A	NM_018135.4	MANE Select	c.422C>G	p.Pro141Arg	missense	Exon 5 of 6	NP_060605.1	Q9NVS2-1
	MRPS18A	NM_001193343.2		c.376+268C>G		intron	N/A	NP_001180272.1	Q9NVS2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPS18A	ENST00000372133.8	TSL:1 MANE Select	c.422C>G	p.Pro141Arg	missense	Exon 5 of 6	ENSP00000361206.3	Q9NVS2-1
MRPS18A	ENST00000427312.1	TSL:1	c.644C>G	p.Pro215Arg	missense	Exon 4 of 5	ENSP00000398679.1	Q5QPA5
MRPS18A	ENST00000924155.1		c.536C>G	p.Pro179Arg	missense	Exon 3 of 4	ENSP00000594214.1

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1569

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0358

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

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:

0.000235

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00344

AC:

620

AN:

180416

AF XY:

0.00253

show subpopulations

Gnomad AFR exome

AF:

0.0359

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.00145

GnomAD4 exome

AF:

0.000954

AC:

1307

AN:

1369396

Hom.:

Cov.:

AF XY:

0.000818

AC XY:

549

AN XY:

671358

show subpopulations

African (AFR)

AF:

0.0346

AC:

1048

AN:

30328

American (AMR)

AF:

0.00230

AC:

AN:

29982

Ashkenazi Jewish (ASJ)

AF:

0.0000498

AC:

AN:

20090

East Asian (EAS)

AF:

0.00

AC:

AN:

38750

South Asian (SAS)

AF:

0.0000142

AC:

AN:

70660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50060

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5240

European-Non Finnish (NFE)

AF:

0.0000496

AC:

AN:

1067976

Other (OTH)

AF:

0.00222

AC:

125

AN:

56310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

126

190

253

316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.0103

AC:

1570

AN:

152236

Hom.:

Cov.:

AF XY:

0.00999

AC XY:

744

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0357

AC:

1483

AN:

41516

American (AMR)

AF:

0.00314

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68026

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

146

218

291

364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.000697

Hom.:

Bravo

AF:

0.0116

ESP6500AA

AF:

0.0306

AC:

135

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00320

AC:

383

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.7

PhyloP100

5.3

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.36

Sift

Uncertain

0.0080

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.54

MVP

0.56

MPC

0.24

ClinPred

0.058

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.78

Mutation Taster

=57/43

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over