Genetic Variant MRPS9:c.135+31C>T (chr2-105038258-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182640.3(MRPS9):c.135+31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,594,610 control chromosomes in the GnomAD database, including 173,639 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 0.49 ( 18177 hom., cov: 32)

Exomes 𝑓: 0.46 ( 155462 hom. )

Consequence

MRPS9
NM_182640.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.234

Publications

10 publications found

Variant links:

Genes affected

MRPS9 (HGNC:14501): (mitochondrial ribosomal protein S9) 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. [provided by RefSeq, Jul 2008]

MRPS9 links:

MRPS9-AS2 (HGNC:40687): (MRPS9 antisense RNA 2)

MRPS9-AS2 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 (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182640.3. 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
	MRPS9	NM_182640.3	MANE Select	c.135+31C>T		intron	N/A	NP_872578.1	P82933
	MRPS9-AS2	NR_110603.1		n.43+196G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MRPS9	ENST00000258455.8	TSL:1 MANE Select	c.135+31C>T	intron	N/A	ENSP00000258455.3	P82933
MRPS9	ENST00000886286.1		c.135+31C>T	intron	N/A	ENSP00000556345.1
MRPS9	ENST00000925255.1		c.135+31C>T	intron	N/A	ENSP00000595314.1

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73730

AN:

151788

Hom.:

18135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.537

Gnomad AMI

AF:

0.337

Gnomad AMR

AF:

0.462

Gnomad ASJ

AF:

0.413

Gnomad EAS

AF:

0.663

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.546

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.471

GnomAD2 exomes

AF:

0.484

AC:

104558

AN:

216128

AF XY:

0.477

show subpopulations

Gnomad AFR exome

AF:

0.536

Gnomad AMR exome

AF:

0.495

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.656

Gnomad FIN exome

AF:

0.549

Gnomad NFE exome

AF:

0.453

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.461

AC:

665803

AN:

1442702

Hom.:

155462

Cov.:

AF XY:

0.459

AC XY:

328855

AN XY:

715794

show subpopulations

African (AFR)

AF:

0.524

AC:

17337

AN:

33086

American (AMR)

AF:

0.483

AC:

20214

AN:

41888

Ashkenazi Jewish (ASJ)

AF:

0.412

AC:

10591

AN:

25688

East Asian (EAS)

AF:

0.703

AC:

27320

AN:

38860

South Asian (SAS)

AF:

0.441

AC:

36865

AN:

83620

European-Finnish (FIN)

AF:

0.542

AC:

28162

AN:

51944

Middle Eastern (MID)

AF:

0.339

AC:

1915

AN:

5648

European-Non Finnish (NFE)

AF:

0.450

AC:

495993

AN:

1102320

Other (OTH)

AF:

0.459

AC:

27406

AN:

59648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

18238

36476

54715

72953

91191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15134

30268

45402

60536

75670

<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:

0.486

AC:

73833

AN:

151908

Hom.:

18177

Cov.:

AF XY:

0.490

AC XY:

36406

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.537

AC:

22272

AN:

41438

American (AMR)

AF:

0.462

AC:

7055

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

1431

AN:

3468

East Asian (EAS)

AF:

0.664

AC:

3408

AN:

5134

South Asian (SAS)

AF:

0.470

AC:

2255

AN:

4800

European-Finnish (FIN)

AF:

0.546

AC:

5753

AN:

10546

Middle Eastern (MID)

AF:

0.315

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.445

AC:

30263

AN:

67940

Other (OTH)

AF:

0.473

AC:

998

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1933

3866

5800

7733

9666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

668

1336

2004

2672

3340

<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:

0.456

Hom.:

3559

Bravo

AF:

0.482

Asia WGS

AF:

0.576

AC:

2003

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.5

(source)

DANN

Benign

0.80

PhyloP100

-0.23

PromoterAI

0.21

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over