Genetic Variant MRPL9:c.589-19_589-5dupTTTTTTTTTTTTTTT (chr1-151760903-C-CAAAAAAAAAAAAAAA) – 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.589-19_589-5dupTTTTTTTTTTTTTTT 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 0.023 ( 157 hom., cov: 0)

Exomes 𝑓: 0.0036 ( 14 hom. )

Failed GnomAD Quality Control

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 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4 link	c.589-19_589-5dupTTTTTTTTTTTTTTT	splice_region_variant, intron_variant	Intron 5 of 6	ENST00000368830.8	NP_113608.1	Q9BYD2
MRPL9	NM_001300733.2 link	c.487-19_487-5dupTTTTTTTTTTTTTTT	splice_region_variant, intron_variant	Intron 4 of 5		NP_001287662.1	Q9BYD2Q5SZR1
MRPL9	NR_125331.2 link	n.646-19_646-5dupTTTTTTTTTTTTTTT	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.589-19_589-5dupTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_031420.4	ENSP00000357823.3		Q9BYD2

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

1679

AN:

74112

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00582

Gnomad AMI

AF:

0.0311

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.0331

Gnomad EAS

AF:

0.00227

Gnomad SAS

AF:

0.0126

Gnomad FIN

AF:

0.00399

Gnomad MID

AF:

0.00893

Gnomad NFE

AF:

0.0346

Gnomad OTH

AF:

0.0255

GnomAD4 exome

AF:

0.00362

AC:

3166

AN:

875472

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

1601

AN XY:

434876

show subpopulations

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

African (AFR)

AF:

0.00135

AC:

AN:

17766

American (AMR)

AF:

0.00227

AC:

AN:

13210

Ashkenazi Jewish (ASJ)

AF:

0.00566

AC:

AN:

13434

East Asian (EAS)

AF:

0.00143

AC:

AN:

29298

South Asian (SAS)

AF:

0.00154

AC:

AN:

43428

European-Finnish (FIN)

AF:

0.00463

AC:

112

AN:

24178

Middle Eastern (MID)

AF:

0.00411

AC:

AN:

2674

European-Non Finnish (NFE)

AF:

0.00384

AC:

2665

AN:

693918

Other (OTH)

AF:

0.00370

AC:

139

AN:

37566

⚠️ 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: 0.332

Heterozygous variant carriers

181

362

544

725

906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0227

AC:

1679

AN:

74106

Hom.:

157

Cov.:

AF XY:

0.0205

AC XY:

694

AN XY:

33918

show subpopulations

African (AFR)

AF:

0.00581

AC:

105

AN:

18076

American (AMR)

AF:

0.0104

AC:

AN:

6532

Ashkenazi Jewish (ASJ)

AF:

0.0331

AC:

AN:

2206

East Asian (EAS)

AF:

0.00228

AC:

AN:

2636

South Asian (SAS)

AF:

0.0127

AC:

AN:

2044

European-Finnish (FIN)

AF:

0.00399

AC:

AN:

2006

Middle Eastern (MID)

AF:

0.00980

AC:

AN:

102

European-Non Finnish (NFE)

AF:

0.0346

AC:

1350

AN:

38968

Other (OTH)

AF:

0.0253

AC:

AN:

990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

106

158

211

264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0106

Hom.:

231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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-CAAAAAAAAAAAAAAAAAAAAAAAAAAA

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