Variant 3-12839404-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000994.4(RPL32):c.223C>T(p.Arg75Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,614,016 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 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

RPL32
NM_000994.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.39

Variant links:

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]

RPL32 links:

ENSG00000289809 (HGNC:):

ENSG00000289809 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26283658).

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL32	NM_000994.4 link	c.223C>T	p.Arg75Trp	missense_variant	3/4	ENST00000429711.7	NP_000985.1	P62910A0A024R2G7
RPL32	NM_001007073.1 link	c.223C>T	p.Arg75Trp	missense_variant	3/4		NP_001007074.1	P62910A0A024R2G7
RPL32	NM_001007074.1 link	c.223C>T	p.Arg75Trp	missense_variant	2/3		NP_001007075.1	P62910A0A024R2G7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL32	ENST00000429711.7 link	c.223C>T	p.Arg75Trp	missense_variant	3/4	1	NM_000994.4	ENSP00000416429.2		P62910
ENSG00000289809	ENST00000454887.1 link	c.267+7832G>A		intron_variant		5		ENSP00000403093.1		C9JH00

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251478

Hom.:

AF XY:

0.0000441

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000447

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:

0.0000432

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.223C>T (p.R75W) alteration is located in exon 2 (coding exon 2) of the RPL32 gene. This alteration results from a C to T substitution at nucleotide position 223, causing the arginine (R) at amino acid position 75 to be replaced by a tryptophan (W). 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

0.72

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Benign

0.95

DEOGEN2

Benign

0.32

T;T;T;T;T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

.;D;D;.;.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.26

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.89

L;L;.;L;L;.

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-4.7

D;D;D;D;D;D

REVEL

Benign

0.17

Sift

Benign

0.18

T;T;T;T;T;T

Sift4G

Benign

0.35

T;T;T;T;T;.

Polyphen

0.0090

B;B;.;B;B;.

Vest4

0.56

MVP

0.32

MPC

0.70

ClinPred

0.30

GERP RS

1.9

Varity_R

0.28

gMVP

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over