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:

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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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MRPS9	NM_182640.3 link	c.135+31C>T	intron_variant	Intron 1 of 10	ENST00000258455.8	NP_872578.1	P82933
MRPS9-AS2	NR_110603.1 link	n.43+196G>A	intron_variant	Intron 1 of 2
MRPS9	XM_047445533.1 link	c.135+31C>T	intron_variant	Intron 1 of 6		XP_047301489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS9	ENST00000258455.8 link	c.135+31C>T		intron_variant	Intron 1 of 10	1	NM_182640.3	ENSP00000258455.3		P82933

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over