Variant 4-108621975-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The ENST00000394667.8(RPL34):c.16A>C(p.Thr6Pro) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T6T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPL34
ENST00000394667.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.89

Variant links:

Genes affected

RPL34 (HGNC:10340): (ribosomal protein L34) 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 L34E family of ribosomal proteins. It is located in the cytoplasm. This gene originally was thought to be located at 17q21, but it has been mapped to 4q. Overexpression of this gene has been observed in some cancer cells. Alternative splicing results in multiple transcript variants, all encoding the same isoform. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Feb 2016]

RPL34 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.752

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL34	NM_001319236.2 linkuse as main transcript	c.16A>C	p.Thr6Pro	missense_variant	2/5	ENST00000394667.8	NP_001306165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL34	ENST00000394667.8 linkuse as main transcript	c.16A>C	p.Thr6Pro	missense_variant	2/5	1	NM_001319236.2	ENSP00000378162	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151826

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.000832

Gnomad FIN

AF:

0.000285

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0172

AC:

23812

AN:

1387564

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

11164

AN XY:

692486

show subpopulations

Gnomad4 AFR exome

AF:

0.0146

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00747

Gnomad4 EAS exome

AF:

0.00502

Gnomad4 SAS exome

AF:

0.00505

Gnomad4 FIN exome

AF:

0.00195

Gnomad4 NFE exome

AF:

0.0206

Gnomad4 OTH exome

AF:

0.0132

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000244

AC:

AN:

151944

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.000833

Gnomad4 FIN

AF:

0.000285

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

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

Apr 08, 2024

The c.16A>C (p.T6P) alteration is located in exon 2 (coding exon 1) of the RPL34 gene. This alteration results from a A to C substitution at nucleotide position 16, causing the threonine (T) at amino acid position 6 to be replaced by a proline (P). 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

0.95

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

D;D;D;D;D

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;.;.;.;D

M_CAP

Uncertain

0.087

MetaRNN

Pathogenic

0.75

D;D;D;D;D

MetaSVM

Uncertain

0.26

MutationAssessor

Pathogenic

3.2

M;M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-4.3

D;D;D;D;D

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D

Polyphen

0.90

P;P;P;P;P

Vest4

0.66

MutPred

0.61

Gain of glycosylation at T6 (P = 0.0069);Gain of glycosylation at T6 (P = 0.0069);Gain of glycosylation at T6 (P = 0.0069);Gain of glycosylation at T6 (P = 0.0069);Gain of glycosylation at T6 (P = 0.0069);

MVP

0.76

MPC

2.1

ClinPred

1.0

GERP RS

5.0

Varity_R

0.87

gMVP

0.90

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