16-89561315-C-T

Variant names:

• chr16-89561315-C-T
• NM_000977.4:c.193C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000977.4(RPL13):​c.193C>T​(p.Arg65Trp) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPL13 NM_000977.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0130

Genes affected

RPL13 (HGNC:10303): (ribosomal protein L13) 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 L13E family of ribosomal proteins. It is located in the cytoplasm. This gene is expressed at significantly higher levels in benign breast lesions than in breast carcinomas. Alternatively spliced transcript variants encoding distinct 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, Jul 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.885

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL13	NM_000977.4	c.193C>T	p.Arg65Trp	missense_variant	Exon 3 of 6	ENST00000311528.10	NP_000968.2
RPL13	NM_033251.2	c.193C>T	p.Arg65Trp	missense_variant	Exon 2 of 5		NP_150254.1
RPL13	NM_001243131.1	c.193C>T	p.Arg65Trp	missense_variant	Exon 3 of 7		NP_001230060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL13	ENST00000311528.10	c.193C>T	p.Arg65Trp	missense_variant	Exon 3 of 6	1	NM_000977.4	ENSP00000307889.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1437364 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 714340

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jan 12, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;T;.;.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.60
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Pathogenic	0.98	.;.;D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.89	D;D;D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	3.5	M;M;M;.;M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.7	D;D;D;.;D
REVEL	Uncertain	0.45
Sift	Pathogenic	0.0	D;D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	D;D;.;.;D
Vest4		0.94
MutPred		0.76		Loss of disorder (P = 0.0051);Loss of disorder (P = 0.0051);Loss of disorder (P = 0.0051);Loss of disorder (P = 0.0051);Loss of disorder (P = 0.0051);
MVP		0.84
MPC		1.5
ClinPred		0.99	D
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.76
gMVP		0.84

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: chr16-89627723;