NM_000977.4:c.530A>C

Variant names:

• chr16-89562936-A-C
• NM_000977.4:c.530A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_000977.4(RPL13):​c.530A>C​(p.Lys177Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPL13 NM_000977.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.21

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.

• PM1: In a modified_residue N6-acetyllysine; alternate (size 0) in uniprot entity RL13_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL13	NM_000977.4	c.530A>C	p.Lys177Thr	missense_variant	Exon 6 of 6	ENST00000311528.10	NP_000968.2
RPL13	NM_033251.2	c.530A>C	p.Lys177Thr	missense_variant	Exon 5 of 5		NP_150254.1
RPL13	NM_001243131.1	c.389A>C	p.Lys130Thr	missense_variant	Exon 7 of 7		NP_001230060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL13	ENST00000311528.10	c.530A>C	p.Lys177Thr	missense_variant	Exon 6 of 6	1	NM_000977.4	ENSP00000307889.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Aug 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.530A>C (p.K177T) alteration is located in exon 1 (coding exon 1) of the RPL13 gene. This alteration results from a A to C substitution at nucleotide position 530, causing the lysine (K) at amino acid position 177 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T;T;T;.;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	.;T;.;T;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.63	D;D;D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L;.;L;.;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Uncertain	0.40
Sift	Benign	0.10	T;D;T;T;T
Sift4G	Benign	0.23	T;T;T;T;T
Polyphen		0.34	B;.;B;.;B
Vest4		0.70
MutPred		0.51		Loss of methylation at K177 (P = 0.0182);.;Loss of methylation at K177 (P = 0.0182);.;Loss of methylation at K177 (P = 0.0182);
MVP		0.79
MPC		0.71
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.38
gMVP		0.53

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: chr16-89629344;