Genetic Variant NM_000661.5:c.259-10_259-7delTTTA (chr4-39456544-TTAAA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000661.5(RPL9):c.259-10_259-7delTTTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 1,612,962 control chromosomes in the GnomAD database, including 1,916 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.029 ( 81 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1835 hom. )

Consequence

RPL9
NM_000661.5 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.52

Variant links:

Genes affected

RPL9 (HGNC:10369): (ribosomal protein L9) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L6P family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

RPL9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 4-39456544-TTAAA-T is Benign according to our data. Variant chr4-39456544-TTAAA-T is described in ClinVar as [Benign]. Clinvar id is 2039467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-39456544-TTAAA-T is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL9	NM_000661.5 link	c.259-10_259-7delTTTA		splice_region_variant, intron_variant	Intron 4 of 7	ENST00000295955.14	NP_000652.2	P32969Q53Z07
RPL9	NM_001024921.4 link	c.259-10_259-7delTTTA		splice_region_variant, intron_variant	Intron 4 of 7		NP_001020092.1	P32969Q53Z07

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL9	ENST00000295955.14 link	c.259-10_259-7delTTTA		splice_region_variant, intron_variant	Intron 4 of 7	1	NM_000661.5	ENSP00000346022.7		P32969

Frequencies

GnomAD3 genomes

AF:

0.0295

AC:

4488

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00827

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0134

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0343

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0501

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0295

AC:

7369

AN:

249680

Hom.:

167

AF XY:

0.0300

AC XY:

4054

AN XY:

135226

show subpopulations

Gnomad AFR exome

AF:

0.00809

Gnomad AMR exome

AF:

0.0151

Gnomad ASJ exome

AF:

0.0245

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.0361

Gnomad NFE exome

AF:

0.0460

Gnomad OTH exome

AF:

0.0280

GnomAD4 exome

AF:

0.0451

AC:

65908

AN:

1460636

Hom.:

1835

AF XY:

0.0442

AC XY:

32116

AN XY:

726548

show subpopulations

Gnomad4 AFR exome

AF:

0.00679

Gnomad4 AMR exome

AF:

0.0153

Gnomad4 ASJ exome

AF:

0.0229

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0117

Gnomad4 FIN exome

AF:

0.0371

Gnomad4 NFE exome

AF:

0.0532

Gnomad4 OTH exome

AF:

0.0382

GnomAD4 genome

AF:

0.0295

AC:

4487

AN:

152326

Hom.:

Cov.:

AF XY:

0.0275

AC XY:

2045

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00825

Gnomad4 AMR

AF:

0.0134

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00787

Gnomad4 FIN

AF:

0.0343

Gnomad4 NFE

AF:

0.0501

Gnomad4 OTH

AF:

0.0165

Alfa

AF:

0.0400

Hom.:

Bravo

AF:

0.0273

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0434

EpiControl

AF:

0.0436

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over