Genetic Variant MRPL9:c.589-18_589-5dupTTTTTTTTTTTTTT (chr1-151760903-C-CAAAAAAAAAAAAAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_031420.4(MRPL9):c.589-18_589-5dupTTTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0024 ( 11 hom. )

Consequence

MRPL9
NM_031420.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.153

Publications

1 publications found

Variant links:

Genes affected

MRPL9 (HGNC:14277): (mitochondrial ribosomal protein L9) This is a nuclear gene encoding a protein component of the 39S subunit of the mitochondrial ribosome. Alternative splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 8. [provided by RefSeq, Jul 2014]

MRPL9 links:

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ACMG classification

Classification was made for transcript

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

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031420.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MRPL9	NM_031420.4	MANE Select	c.589-18_589-5dupTTTTTTTTTTTTTT	splice_region intron	N/A	NP_113608.1
MRPL9	NM_001300733.2		c.487-18_487-5dupTTTTTTTTTTTTTT	splice_region intron	N/A	NP_001287662.1
MRPL9	NR_125331.2		n.646-18_646-5dupTTTTTTTTTTTTTT	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MRPL9	ENST00000368830.8	TSL:1 MANE Select	c.589-18_589-5dupTTTTTTTTTTTTTT	splice_region intron	N/A	ENSP00000357823.3
MRPL9	ENST00000495867.1	TSL:2	n.4_17dupTTTTTTTTTTTTTT	non_coding_transcript_exon	Exon 1 of 2
MRPL9	ENST00000368829.3	TSL:2	c.487-18_487-5dupTTTTTTTTTTTTTT	splice_region intron	N/A	ENSP00000357822.3

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

74202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000153

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:

0.000410

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00244

AC:

2138

AN:

876744

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

1108

AN XY:

435514

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000732

AC:

AN:

17768

American (AMR)

AF:

0.000832

AC:

AN:

13216

Ashkenazi Jewish (ASJ)

AF:

0.00305

AC:

AN:

13432

East Asian (EAS)

AF:

0.000443

AC:

AN:

29330

South Asian (SAS)

AF:

0.00157

AC:

AN:

43448

European-Finnish (FIN)

AF:

0.00346

AC:

AN:

24250

Middle Eastern (MID)

AF:

0.00300

AC:

AN:

2668

European-Non Finnish (NFE)

AF:

0.00260

AC:

1806

AN:

694970

Other (OTH)

AF:

0.00250

AC:

AN:

37662

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.337

Heterozygous variant carriers

124

247

371

494

618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.000256

AC:

AN:

74196

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33962

show subpopulations

African (AFR)

AF:

0.000111

AC:

AN:

18078

American (AMR)

AF:

0.000153

AC:

AN:

6542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2212

East Asian (EAS)

AF:

0.00

AC:

AN:

2640

South Asian (SAS)

AF:

0.00

AC:

AN:

2044

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

102

European-Non Finnish (NFE)

AF:

0.000410

AC:

AN:

39032

Other (OTH)

AF:

0.00

AC:

AN:

994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00

Hom.:

231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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