rs1553121574

Positions:

• chr1-23691827-G-A
• chr1-23691827-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_000975.5(RPL11):​c.4G>A​(p.Ala2Thr) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPL11 NM_000975.5 missense, splice_region
• Scores: Splicing: ADA: 0.9097
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.61

Genes affected

RPL11 (HGNC:10301): (ribosomal protein L11) 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 L5P family of ribosomal proteins. It is located in the cytoplasm. The protein probably associates with the 5S rRNA. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a chain 60S ribosomal protein L11 (size 176) in uniprot entity RL11_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_000975.5
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4152902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL11	NM_000975.5	c.4G>A	p.Ala2Thr	missense_variant, splice_region_variant	1/6	ENST00000643754.2	NP_000966.2
RPL11	NM_001199802.1	c.4G>A	p.Ala2Thr	missense_variant, splice_region_variant	1/6		NP_001186731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL11	ENST00000643754.2	c.4G>A	p.Ala2Thr	missense_variant, splice_region_variant	1/6		NM_000975.5	ENSP00000496250	A1
RPL11	ENST00000374550.8	c.4G>A	p.Ala2Thr	missense_variant, splice_region_variant	1/6	1		ENSP00000363676	P4
RPL11	ENST00000443624.6	n.22G>A		splice_region_variant, non_coding_transcript_exon_variant	1/5	2
RPL11	ENST00000467075.2	c.4G>A	p.Ala2Thr	missense_variant, NMD_transcript_variant	1/6	3		ENSP00000493634

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	.;T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.3	L;L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.67	N;.
REVEL	Uncertain	0.41
Sift	Benign	0.050	D;.
Sift4G	Benign	0.17	T;.
Polyphen		0.0050	B;B
Vest4		0.60
MutPred		0.12		Gain of glycosylation at A2 (P = 0.0306);Gain of glycosylation at A2 (P = 0.0306);
MVP		0.97
MPC		0.70
ClinPred		0.82	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.91
dbscSNV1_RF	Pathogenic	0.80
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

LitVar

Other links and lift over

dbSNP: rs1553121574; hg19: chr1-24018317;