4-39454615-G-C

Variant names:

• chr4-39454615-G-C
• NM_000661.5:c.507C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000661.5(RPL9):​c.507C>G​(p.Asn169Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPL9 NM_000661.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.00

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35449153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL9	NM_000661.5	c.507C>G	p.Asn169Lys	missense_variant	Exon 7 of 8	ENST00000295955.14	NP_000652.2
RPL9	NM_001024921.4	c.507C>G	p.Asn169Lys	missense_variant	Exon 7 of 8		NP_001020092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL9	ENST00000295955.14	c.507C>G	p.Asn169Lys	missense_variant	Exon 7 of 8	1	NM_000661.5	ENSP00000346022.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.507C>G (p.N169K) alteration is located in exon 6 (coding exon 6) of the RPL9 gene. This alteration results from a C to G substitution at nucleotide position 507, causing the asparagine (N) at amino acid position 169 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.24	T;T;.;T;.;.;T
Eigen	Benign	0.0018
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.92	.;.;D;D;D;D;D
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.35	T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M;M;.;M;.;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.7	.;D;.;D;.;.;D
REVEL	Benign	0.075
Sift	Benign	0.15	.;T;.;T;.;.;T
Sift4G	Benign	0.20	.;T;.;T;.;T;.
Polyphen		0.013	B;B;.;B;.;.;.
Vest4		0.36, 0.37
MutPred		0.47		Gain of methylation at N169 (P = 0.0062);Gain of methylation at N169 (P = 0.0062);.;Gain of methylation at N169 (P = 0.0062);.;.;.;
MVP		0.48
MPC		1.1
ClinPred		0.75	D
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-39456235;