Genetic Variant NM_031420.4:c.589-10_589-5dupTTTTTT (chr1-151760903-C-CAAAAAA) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_031420.4(MRPL9):c.589-10_589-5dupTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 11 hom., cov: 0)

Exomes 𝑓: 0.00059 ( 1 hom. )

Consequence

MRPL9
NM_031420.4 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 1-151760903-C-CAAAAAA is Benign according to our data. Variant chr1-151760903-C-CAAAAAA is described in ClinVar as [Likely_benign]. Clinvar id is 3388833.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4 link	c.589-10_589-5dupTTTTTT	splice_region_variant, intron_variant	Intron 5 of 6	ENST00000368830.8	NP_113608.1	Q9BYD2
MRPL9	NM_001300733.2 link	c.487-10_487-5dupTTTTTT	splice_region_variant, intron_variant	Intron 4 of 5		NP_001287662.1	Q9BYD2Q5SZR1
MRPL9	NR_125331.2 link	n.646-10_646-5dupTTTTTT	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.589-10_589-5dupTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_031420.4	ENSP00000357823.3		Q9BYD2

Frequencies

GnomAD3 genomes

AF:

0.00182

AC:

135

AN:

74192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00687

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000764

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:

0.000102

Gnomad OTH

AF:

0.00203

GnomAD4 exome

AF:

0.000589

AC:

518

AN:

879114

Hom.:

Cov.:

AF XY:

0.000650

AC XY:

284

AN XY:

436744

show subpopulations

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

African (AFR)

AF:

0.00231

AC:

AN:

17734

American (AMR)

AF:

0.00166

AC:

AN:

13246

Ashkenazi Jewish (ASJ)

AF:

0.000739

AC:

AN:

13524

East Asian (EAS)

AF:

0.000476

AC:

AN:

29392

South Asian (SAS)

AF:

0.00108

AC:

AN:

43438

European-Finnish (FIN)

AF:

0.000737

AC:

AN:

24414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2678

European-Non Finnish (NFE)

AF:

0.000479

AC:

334

AN:

696884

Other (OTH)

AF:

0.000846

AC:

AN:

37804

⚠️ 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: 0.342

Heterozygous variant carriers

105

140

175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00182

AC:

135

AN:

74184

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

AN XY:

33958

show subpopulations

African (AFR)

AF:

0.00686

AC:

124

AN:

18072

American (AMR)

AF:

0.000764

AC:

AN:

6544

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2210

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:

100

European-Non Finnish (NFE)

AF:

0.000102

AC:

AN:

39028

Other (OTH)

AF:

0.00201

AC:

AN:

994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.548

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

231

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MRPL9: BP4, BS2 -

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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NM_031420.4:c.589-10_589-5dupTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over