chr4-39454922-T-G

Variant names:

• chr4-39454922-T-G
• rs200690365
• NM_000661.5:c.414A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000661.5(RPL9):​c.414A>C​(p.Gln138His) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q138Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPL9 NM_000661.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.509
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26157835).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000661.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL9	NM_000661.5	MANE Select	c.414A>C	p.Gln138His	missense	Exon 6 of 8	NP_000652.2
	RPL9	NM_001024921.4		c.414A>C	p.Gln138His	missense	Exon 6 of 8	NP_001020092.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL9	ENST00000295955.14	TSL:1 MANE Select	c.414A>C	p.Gln138His	missense	Exon 6 of 8	ENSP00000346022.7
	RPL9	ENST00000449470.6	TSL:1	c.414A>C	p.Gln138His	missense	Exon 5 of 7	ENSP00000400467.2
	RPL9	ENST00000503277.6	TSL:2	c.498A>C	p.Gln166His	missense	Exon 5 of 7	ENSP00000494836.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.096
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		0.51
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.12
Sift	Benign	0.036	D
Sift4G	Benign	0.066	T
Polyphen		0.39	B
Vest4		0.33
MutPred		0.27		Gain of ubiquitination at K141 (P = 0.0898)
MVP		0.70
MPC		1.6
ClinPred		0.94	D
GERP RS		4.3
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.15
gMVP		0.68
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs200690365; hg19: chr4-39456542;