3-12839491-G-T

Position:

• chr3-12839491-G-T

Variant summary

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

The NM_000994.4(RPL32):​c.136C>A​(p.Arg46Ser) variant causes a missense change involving the alteration of a 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)
• Consequence: RPL32 NM_000994.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.46

Genes affected

RPL32 (HGNC:10336): (ribosomal protein L32) 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 L32E family of ribosomal proteins. It is located in the cytoplasm. Although some studies have mapped this gene to 3q13.3-q21, it is believed to map to 3p25-p24. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding the same protein have been observed for this gene. [provided by RefSeq, Jul 2008]

ENSG00000289809 (HGNC:):

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, 0.903

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL32	NM_000994.4	c.136C>A	p.Arg46Ser	missense_variant	3/4	ENST00000429711.7	NP_000985.1
RPL32	NM_001007073.1	c.136C>A	p.Arg46Ser	missense_variant	3/4		NP_001007074.1
RPL32	NM_001007074.1	c.136C>A	p.Arg46Ser	missense_variant	2/3		NP_001007075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL32	ENST00000429711.7	c.136C>A	p.Arg46Ser	missense_variant	3/4	1	NM_000994.4	ENSP00000416429.2
ENSG00000289809	ENST00000454887.1	c.267+7919G>T		intron_variant		5		ENSP00000403093.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2023

The c.136C>A (p.R46S) alteration is located in exon 2 (coding exon 2) of the RPL32 gene. This alteration results from a C to A substitution at nucleotide position 136, causing the arginine (R) at amino acid position 46 to be replaced by a serine (S). 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	1.0
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D;D;T;D;D;T;T
Eigen	Benign	-0.050
Eigen_PC	Benign	-0.092
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.72	.;T;T;.;.;T;T
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.90	D;D;D;D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Pathogenic	3.0	M;M;.;M;M;.;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-3.9	D;D;D;D;D;D;D
REVEL	Uncertain	0.38
Sift	Benign	0.039	D;D;D;D;D;D;T
Sift4G	Uncertain	0.023	D;D;D;D;D;.;D
Polyphen		0.49	P;P;.;P;P;.;.
Vest4		0.87
MutPred		0.86		Gain of phosphorylation at R46 (P = 0.0165);Gain of phosphorylation at R46 (P = 0.0165);.;Gain of phosphorylation at R46 (P = 0.0165);Gain of phosphorylation at R46 (P = 0.0165);Gain of phosphorylation at R46 (P = 0.0165);Gain of phosphorylation at R46 (P = 0.0165);
MVP		0.68
MPC		0.95
ClinPred		0.99	D
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.60
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr3-12880990;