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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4 link	c.589-23_589-5dupTTTTTTTTTTTTTTTTTTT	splice_region_variant, intron_variant	Intron 5 of 6	ENST00000368830.8	NP_113608.1	Q9BYD2
MRPL9	NM_001300733.2 link	c.487-23_487-5dupTTTTTTTTTTTTTTTTTTT	splice_region_variant, intron_variant	Intron 4 of 5		NP_001287662.1	Q9BYD2Q5SZR1
MRPL9	NR_125331.2 link	n.646-23_646-5dupTTTTTTTTTTTTTTTTTTT	splice_region_variant, intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL9	ENST00000368830.8 link	c.589-5_589-4insTTTTTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_031420.4	ENSP00000357823.3		Q9BYD2

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 = 0.000000), 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

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over