rs555027604

Variant names:

• chr17-38850183-C-G
• NM_000978.4:c.372G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-38850183-C-G
• chr17-38850183-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000978.4(RPL23):​c.372G>C​(p.Glu124Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RPL23 NM_000978.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

Genes affected

RPL23 (HGNC:10316): (ribosomal protein L23) 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 L14P family of ribosomal proteins. It is located in the cytoplasm. This gene has been referred to as rpL17 because the encoded protein shares amino acid identity with ribosomal protein L17 from Saccharomyces cerevisiae; however, its official symbol is RPL23. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.945

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL23	NM_000978.4	c.372G>C	p.Glu124Asp	missense_variant	Exon 5 of 5	ENST00000479035.7	NP_000969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL23	ENST00000479035.7	c.372G>C	p.Glu124Asp	missense_variant	Exon 5 of 5	1	NM_000978.4	ENSP00000420311.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455160 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723744

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D;D;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.93	.;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Pathogenic	4.1	H;H;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.9	D;D;.
REVEL	Uncertain	0.35
Sift	Uncertain	0.0040	D;D;.
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.62	P;P;.
Vest4		0.81
MutPred		0.90		Loss of ubiquitination at K123 (P = 0.045);Loss of ubiquitination at K123 (P = 0.045);.;
MVP		0.58
MPC		1.9
ClinPred		1.0	D
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-37006436;