Variant 4-39456431-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000295955.14(RPL9):c.366T>C(p.Tyr122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 1,612,904 control chromosomes in the GnomAD database, including 391,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33954 hom., cov: 32)

Exomes 𝑓: 0.70 ( 357805 hom. )

Consequence

RPL9
ENST00000295955.14 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.22

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 4-39456431-A-G is Benign according to our data. Variant chr4-39456431-A-G is described in ClinVar as [Benign]. Clinvar id is 1265779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL9	NM_000661.5 linkuse as main transcript	c.366T>C	p.Tyr122=	synonymous_variant	5/8	ENST00000295955.14	NP_000652.2
RPL9	NM_001024921.4 linkuse as main transcript	c.366T>C	p.Tyr122=	synonymous_variant	5/8		NP_001020092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL9	ENST00000295955.14 linkuse as main transcript	c.366T>C	p.Tyr122=	synonymous_variant	5/8	1	NM_000661.5	ENSP00000346022	P1

Frequencies

GnomAD3 genomes

AF:

0.664

AC:

100888

AN:

151894

Hom.:

33924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.551

Gnomad AMI

AF:

0.835

Gnomad AMR

AF:

0.762

Gnomad ASJ

AF:

0.709

Gnomad EAS

AF:

0.735

Gnomad SAS

AF:

0.773

Gnomad FIN

AF:

0.645

Gnomad MID

AF:

0.672

Gnomad NFE

AF:

0.695

Gnomad OTH

AF:

0.687

GnomAD3 exomes

AF:

0.708

AC:

177868

AN:

251158

Hom.:

63572

AF XY:

0.710

AC XY:

96503

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.540

Gnomad AMR exome

AF:

0.794

Gnomad ASJ exome

AF:

0.696

Gnomad EAS exome

AF:

0.733

Gnomad SAS exome

AF:

0.779

Gnomad FIN exome

AF:

0.651

Gnomad NFE exome

AF:

0.695

Gnomad OTH exome

AF:

0.713

GnomAD4 exome

AF:

0.698

AC:

1020093

AN:

1460892

Hom.:

357805

Cov.:

AF XY:

0.700

AC XY:

508940

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.542

Gnomad4 AMR exome

AF:

0.791

Gnomad4 ASJ exome

AF:

0.702

Gnomad4 EAS exome

AF:

0.729

Gnomad4 SAS exome

AF:

0.769

Gnomad4 FIN exome

AF:

0.653

Gnomad4 NFE exome

AF:

0.696

Gnomad4 OTH exome

AF:

0.688

GnomAD4 genome

AF:

0.664

AC:

100974

AN:

152012

Hom.:

33954

Cov.:

AF XY:

0.665

AC XY:

49401

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.551

Gnomad4 AMR

AF:

0.763

Gnomad4 ASJ

AF:

0.709

Gnomad4 EAS

AF:

0.736

Gnomad4 SAS

AF:

0.773

Gnomad4 FIN

AF:

0.645

Gnomad4 NFE

AF:

0.695

Gnomad4 OTH

AF:

0.692

Alfa

AF:

0.683

Hom.:

11493

Bravo

AF:

0.668

Asia WGS

AF:

0.771

AC:

2683

AN:

3478

EpiCase

AF:

0.698

EpiControl

AF:

0.703

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.3

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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