Genetic Variant MRPL9:c.589-23_589-5dupTTTTTTTTTTTTTTTTTTT (chr1-151760903-C-CAAAAAAAAAAAAAAAAAAA) – 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.589-23_589-5dupTTTTTTTTTTTTTTTTTTT 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 0.00036 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00038 ( 4 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 4 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.589-23_589-5dupTTTTTTTTTTTTTTTTTTT	splice_region intron	N/A	NP_113608.1
MRPL9	NM_001300733.2		c.487-23_487-5dupTTTTTTTTTTTTTTTTTTT	splice_region intron	N/A	NP_001287662.1
MRPL9	NR_125331.2		n.646-23_646-5dupTTTTTTTTTTTTTTTTTTT	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MRPL9	ENST00000368830.8	TSL:1 MANE Select	c.589-5_589-4insTTTTTTTTTTTTTTTTTTT	splice_region intron	N/A	ENSP00000357823.3
MRPL9	ENST00000368829.3	TSL:2	c.487-5_487-4insTTTTTTTTTTTTTTTTTTT	splice_region intron	N/A	ENSP00000357822.3
MRPL9	ENST00000495867.1	TSL:2	n.17_18insTTTTTTTTTTTTTTTTTTT	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000377

AC:

AN:

74202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000222

Gnomad AMI

AF:

0.00183

Gnomad AMR

AF:

0.000611

Gnomad ASJ

AF:

0.000452

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00893

Gnomad NFE

AF:

0.000435

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000375

AC:

330

AN:

879288

Hom.:

Cov.:

AF XY:

0.000408

AC XY:

178

AN XY:

436800

show subpopulations

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

African (AFR)

AF:

0.000563

AC:

AN:

17772

American (AMR)

AF:

0.000151

AC:

AN:

13248

Ashkenazi Jewish (ASJ)

AF:

0.000888

AC:

AN:

13518

East Asian (EAS)

AF:

0.0000681

AC:

AN:

29386

South Asian (SAS)

AF:

0.000529

AC:

AN:

43456

European-Finnish (FIN)

AF:

0.000328

AC:

AN:

24396

Middle Eastern (MID)

AF:

0.00112

AC:

AN:

2682

European-Non Finnish (NFE)

AF:

0.000364

AC:

254

AN:

697000

Other (OTH)

AF:

0.000423

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: 0.371

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:

0.000364

AC:

AN:

74196

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

AN XY:

33962

show subpopulations

African (AFR)

AF:

0.000221

AC:

AN:

18076

American (AMR)

AF:

0.000611

AC:

AN:

6544

Ashkenazi Jewish (ASJ)

AF:

0.000452

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:

0.000436

AC:

AN:

39032

Other (OTH)

AF:

0.00

AC:

AN:

994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-151760903-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

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