16-89562903-C-T

Variant names:

• chr16-89562903-C-T
• rs61734766
• NM_000977.4:c.497C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_000977.4(RPL13):​c.497C>T​(p.Ala166Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,581,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00049 (0 hom.)
• Consequence: RPL13 NM_000977.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.113203585).
• BS2: High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL13	NM_000977.4	c.497C>T	p.Ala166Val	missense_variant	Exon 6 of 6	ENST00000311528.10	NP_000968.2
RPL13	NM_033251.2	c.497C>T	p.Ala166Val	missense_variant	Exon 5 of 5		NP_150254.1
RPL13	NM_001243131.1	c.356C>T	p.Ala119Val	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.497C>T	p.Ala166Val	missense_variant	Exon 6 of 6	1	NM_000977.4	ENSP00000307889.5

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000357 AC: 80 AN: 223876 Hom.: 0 AF XY: 0.000336 AC XY: 41 AN XY: 121952

Gnomad AFR exome AF: 0.000202

Gnomad AMR exome AF: 0.000182

Gnomad ASJ exome AF: 0.000559

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000387

Gnomad FIN exome AF: 0.0000474

Gnomad NFE exome AF: 0.000610

Gnomad OTH exome AF: 0.000189

GnomAD4 exome AF: 0.000485 AC: 694 AN: 1429628 Hom.: 0 Cov.: 31 AF XY: 0.000462 AC XY: 328 AN XY: 710226

Gnomad4 AFR exome AF: 0.0000320

Gnomad4 AMR exome AF: 0.000159

Gnomad4 ASJ exome AF: 0.000998

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000245

Gnomad4 FIN exome AF: 0.0000757

Gnomad4 NFE exome AF: 0.000561

Gnomad4 OTH exome AF: 0.000577

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152310 Hom.: 0 Cov.: 33 AF XY: 0.000269 AC XY: 20 AN XY: 74470

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000532 Hom.: 0

Bravo AF: 0.000268

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000338 AC: 41

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

May 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.497C>T (p.A166V) alteration is located in exon 1 (coding exon 1) of the RPL13 gene. This alteration results from a C to T substitution at nucleotide position 497, causing the alanine (A) at amino acid position 166 to be replaced by a valine (V). 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	Pathogenic	0.69
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;T;T;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.23
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	.;T;.;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;M;.;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.3	D;D;D;D;D
REVEL	Benign	0.21
Sift	Benign	0.19	T;D;T;T;T
Sift4G	Benign	0.28	T;T;T;T;T
Polyphen		0.12	B;.;B;.;B
Vest4		0.49
MVP		0.74
MPC		0.26
ClinPred		0.11	T
GERP RS		3.5
Varity_R		0.40
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs61734766; hg19: chr16-89629311;