Genetic Variant MRPL9:c.589-14_589-5dupTTTTTTTTTT (chr1-151760903-C-CAAAAAAAAAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The ENST00000368830.8(MRPL9):c.589-14_589-5dupTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00012 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

MRPL9
ENST00000368830.8 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 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368830.8. 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.589-14_589-5dupTTTTTTTTTT	splice_region intron	N/A	NP_113608.1
MRPL9	NM_001300733.2		c.487-14_487-5dupTTTTTTTTTT	splice_region intron	N/A	NP_001287662.1
MRPL9	NR_125331.2		n.646-14_646-5dupTTTTTTTTTT	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MRPL9	ENST00000368830.8	TSL:1 MANE Select	c.589-14_589-5dupTTTTTTTTTT	splice_region intron	N/A	ENSP00000357823.3
MRPL9	ENST00000495867.1	TSL:2	n.8_17dupTTTTTTTTTT	non_coding_transcript_exon	Exon 1 of 2
MRPL9	ENST00000368829.3	TSL:2	c.487-14_487-5dupTTTTTTTTTT	splice_region intron	N/A	ENSP00000357822.3

Frequencies

GnomAD3 genomes

AF:

0.000121

AC:

AN:

74202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000332

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000768

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000196

AC:

172

AN:

879546

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

AN XY:

436928

show subpopulations

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

African (AFR)

AF:

0.000281

AC:

AN:

17786

American (AMR)

AF:

0.000226

AC:

AN:

13252

Ashkenazi Jewish (ASJ)

AF:

0.0000739

AC:

AN:

13534

East Asian (EAS)

AF:

0.000136

AC:

AN:

29396

South Asian (SAS)

AF:

0.000299

AC:

AN:

43462

European-Finnish (FIN)

AF:

0.000287

AC:

AN:

24414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2682

European-Non Finnish (NFE)

AF:

0.000191

AC:

133

AN:

697190

Other (OTH)

AF:

0.000159

AC:

AN:

37830

⚠️ 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: 0.352

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000121

AC:

AN:

74196

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

33962

show subpopulations

African (AFR)

AF:

0.000332

AC:

AN:

18078

American (AMR)

AF:

0.00

AC:

AN:

6544

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:

2042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

102

European-Non Finnish (NFE)

AF:

0.0000769

AC:

AN:

39032

Other (OTH)

AF:

0.00

AC:

AN:

994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

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