16-89562335-G-C

Variant names:

• chr16-89562335-G-C
• NM_000977.4:c.421G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000977.4(RPL13):​c.421G>C​(p.Ala141Pro) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,460,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RPL13 NM_000977.4 missense, splice_region
• Scores: Splicing: ADA: 0.02133
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1964486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL13	NM_000977.4	c.421G>C	p.Ala141Pro	missense_variant, splice_region_variant	Exon 5 of 6	ENST00000311528.10	NP_000968.2
RPL13	NM_033251.2	c.421G>C	p.Ala141Pro	missense_variant, splice_region_variant	Exon 4 of 5		NP_150254.1
RPL13	NM_001243131.1	c.280G>C	p.Ala94Pro	missense_variant, splice_region_variant	Exon 6 of 7		NP_001230060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL13	ENST00000311528.10	c.421G>C	p.Ala141Pro	missense_variant, splice_region_variant	Exon 5 of 6	1	NM_000977.4	ENSP00000307889.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460916 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726772

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.038	T;T;.;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.93	.;.;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;.;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.27	T;T;T;T
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.0020	B;B;.;B
Vest4		0.22
MutPred		0.66		Gain of glycosylation at A141 (P = 0.1369);Gain of glycosylation at A141 (P = 0.1369);.;Gain of glycosylation at A141 (P = 0.1369);
MVP		0.24
MPC		0.35
ClinPred		0.40	T
GERP RS		3.5
Varity_R		0.61
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.021
dbscSNV1_RF	Benign	0.34
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: chr16-89628743;