Genetic Variant NM_031420.4:c.589-6_589-5dupTT (chr1-151760903-C-CAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_031420.4(MRPL9):c.589-6_589-5dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 1889 hom., cov: 0)

Exomes 𝑓: 0.099 ( 482 hom. )

Consequence

MRPL9
NM_031420.4 splice_region, intron

Scores

Not classified

Clinical Significance

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: Benign. The variant received -10 ACMG points.

BP6

Variant 1-151760903-C-CAA is Benign according to our data. Variant chr1-151760903-C-CAA is described in ClinVar as [Benign]. Clinvar id is 403108.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

14017

AN:

74010

Hom.:

1891

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.0982

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.160

GnomAD4 exome

AF:

0.0994

AC:

83209

AN:

836750

Hom.:

482

Cov.:

AF XY:

0.0987

AC XY:

41054

AN XY:

415996

show subpopulations

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

African (AFR)

AF:

0.145

AC:

2421

AN:

16664

American (AMR)

AF:

0.113

AC:

1416

AN:

12586

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

1359

AN:

12688

East Asian (EAS)

AF:

0.0806

AC:

2197

AN:

27260

South Asian (SAS)

AF:

0.0848

AC:

3596

AN:

42406

European-Finnish (FIN)

AF:

0.120

AC:

2742

AN:

22892

Middle Eastern (MID)

AF:

0.0960

AC:

243

AN:

2532

European-Non Finnish (NFE)

AF:

0.0988

AC:

65562

AN:

663912

Other (OTH)

AF:

0.103

AC:

3673

AN:

35810

⚠️ 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: 0.344

Heterozygous variant carriers

4818

9637

14455

19274

24092

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.189

AC:

14013

AN:

74002

Hom.:

1889

Cov.:

AF XY:

0.187

AC XY:

6324

AN XY:

33870

show subpopulations

African (AFR)

AF:

0.268

AC:

4825

AN:

18004

American (AMR)

AF:

0.152

AC:

990

AN:

6534

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

278

AN:

2212

East Asian (EAS)

AF:

0.133

AC:

349

AN:

2628

South Asian (SAS)

AF:

0.122

AC:

249

AN:

2038

European-Finnish (FIN)

AF:

0.160

AC:

320

AN:

1996

Middle Eastern (MID)

AF:

0.0882

AC:

AN:

102

European-Non Finnish (NFE)

AF:

0.172

AC:

6685

AN:

38956

Other (OTH)

AF:

0.159

AC:

157

AN:

990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

459

919

1378

1838

2297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0572

Hom.:

231

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(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.589-6_589-5dupTT

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