4-39456431-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000661.5(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 NM_000661.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.22

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]

ACMG classification

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	UniProt
RPL9	NM_000661.5	c.366T>C	p.Tyr122=	synonymous_variant	5/8	ENST00000295955.14
RPL9	NM_001024921.4	c.366T>C	p.Tyr122=	synonymous_variant	5/8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100888 AN: 151894 Hom.: 33924 Cov.: 32

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

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.: 46 AF XY: 0.700 AC XY: 508940 AN XY: 726774

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.: 32 AF XY: 0.665 AC XY: 49401 AN XY: 74312

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
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

Other links and lift over

dbSNP: rs2125313; hg19: chr4-39458051; COSMIC: COSV54696456; COSMIC: COSV54696456;