Variant 4-108621979-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The ENST00000394667.8(RPL34):c.20A>C(p.Tyr7Ser) 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 (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 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 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.884

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL34	NM_001319236.2 linkuse as main transcript	c.20A>C	p.Tyr7Ser	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.20A>C	p.Tyr7Ser	missense_variant	2/5	1	NM_001319236.2	ENSP00000378162	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152144

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00161

AC:

2333

AN:

1453310

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

1074

AN XY:

723230

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000728

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.000465

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00194

Gnomad4 OTH exome

AF:

0.00125

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000525

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

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

Jan 10, 2023

The c.20A>C (p.Y7S) 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 20, causing the tyrosine (Y) at amino acid position 7 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

0.97

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;T;T;T;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

.;.;.;.;D

M_CAP

Benign

0.068

MetaRNN

Pathogenic

0.88

D;D;D;D;D

MetaSVM

Uncertain

0.049

MutationAssessor

Pathogenic

3.1

M;M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-6.3

D;D;D;D;D

REVEL

Pathogenic

0.73

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Uncertain

0.010

D;D;D;D;D

Polyphen

0.67

P;P;P;P;P

Vest4

0.87

MutPred

0.73

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

1.3

ClinPred

1.0

GERP RS

5.0

Varity_R

0.92

gMVP

0.92

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