Genetic Variant MRPL9:c.589-9_589-5dupTTTTT (chr1-151760903-C-CAAAAA) – 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.589-9_589-5dupTTTTT 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 0.00074 ( 2 hom., cov: 0)

Exomes 𝑓: 0.0025 ( 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 GnomAd4 at 2 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.589-9_589-5dupTTTTT	splice_region intron	N/A	NP_113608.1
MRPL9	NM_001300733.2		c.487-9_487-5dupTTTTT	splice_region intron	N/A	NP_001287662.1
MRPL9	NR_125331.2		n.646-9_646-5dupTTTTT	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MRPL9	ENST00000368830.8	TSL:1 MANE Select	c.589-9_589-5dupTTTTT	splice_region intron	N/A	ENSP00000357823.3
MRPL9	ENST00000495867.1	TSL:2	n.13_17dupTTTTT	non_coding_transcript_exon	Exon 1 of 2
MRPL9	ENST00000368829.3	TSL:2	c.487-9_487-5dupTTTTT	splice_region intron	N/A	ENSP00000357822.3

Frequencies

GnomAD3 genomes

AF:

0.000755

AC:

AN:

74166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000612

Gnomad ASJ

AF:

0.000453

Gnomad EAS

AF:

0.000377

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000513

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00254

AC:

2231

AN:

877068

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

1125

AN XY:

435670

show subpopulations

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

African (AFR)

AF:

0.00447

AC:

AN:

17672

American (AMR)

AF:

0.00568

AC:

AN:

13194

Ashkenazi Jewish (ASJ)

AF:

0.00334

AC:

AN:

13486

East Asian (EAS)

AF:

0.00273

AC:

AN:

29286

South Asian (SAS)

AF:

0.00392

AC:

170

AN:

43386

European-Finnish (FIN)

AF:

0.00242

AC:

AN:

24338

Middle Eastern (MID)

AF:

0.00562

AC:

AN:

2670

European-Non Finnish (NFE)

AF:

0.00229

AC:

1590

AN:

695308

Other (OTH)

AF:

0.00313

AC:

118

AN:

37728

⚠️ 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: 0.327

Heterozygous variant carriers

165

330

496

661

826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

116

174

232

290

<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:

0.000742

AC:

AN:

74160

Hom.:

Cov.:

AF XY:

0.000619

AC XY:

AN XY:

33950

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

18068

American (AMR)

AF:

0.000611

AC:

AN:

6542

Ashkenazi Jewish (ASJ)

AF:

0.000453

AC:

AN:

2208

East Asian (EAS)

AF:

0.000379

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:

100

European-Non Finnish (NFE)

AF:

0.000513

AC:

AN:

39014

Other (OTH)

AF:

0.00

AC:

AN:

992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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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1-151760903-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAA

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