1-23692632-C-A

Variant names:

• chr1-23692632-C-A
• rs139286202
• NM_000975.5:c.30C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000975.5(RPL11):​c.30C>A​(p.Asn10Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N10Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPL11 NM_000975.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69
• Publications: 2 publications found

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]

RPL11 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 7

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.907

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL11	NM_000975.5	c.30C>A	p.Asn10Lys	missense_variant	Exon 2 of 6	ENST00000643754.2	NP_000966.2
RPL11	NM_001199802.1	c.27C>A	p.Asn9Lys	missense_variant	Exon 2 of 6		NP_001186731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL11	ENST00000643754.2	c.30C>A	p.Asn10Lys	missense_variant	Exon 2 of 6		NM_000975.5	ENSP00000496250.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	.;T
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Pathogenic	4.0	.;H
PhyloP100		3.7
PrimateAI	Pathogenic	0.90	D
REVEL	Pathogenic	0.77
Polyphen		0.99	D;D
MutPred		0.79		.;Gain of ubiquitination at N10 (P = 0.0177);
MVP		0.85
MPC		1.9
ClinPred		1.0	D
GERP RS		4.2
PromoterAI		0.0044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.96
gMVP		0.95
Mutation Taster		=31/69	disease causing

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: rs139286202; hg19: chr1-24019122;