4-108621977-A-C

Position:

• chr4-108621977-A-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001319236.2(RPL34):​c.18A>C​(p.Thr6Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 33)
  • Exomes 𝑓: 0.014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPL34 NM_001319236.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.28

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-108621977-A-C is Benign according to our data. Variant chr4-108621977-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2655019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.28 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL34	NM_001319236.2	c.18A>C	p.Thr6Thr	synonymous_variant	2/5	ENST00000394667.8	NP_001306165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL34	ENST00000394667.8	c.18A>C	p.Thr6Thr	synonymous_variant	2/5	1	NM_001319236.2	ENSP00000378162.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 47 AN: 151866 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000285

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0143 AC: 20148 AN: 1405828 Hom.: 0 Cov.: 29 AF XY: 0.0135 AC XY: 9464 AN XY: 700872

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.00124

Gnomad4 ASJ exome AF: 0.00714

Gnomad4 EAS exome AF: 0.00588

Gnomad4 SAS exome AF: 0.00411

Gnomad4 FIN exome AF: 0.00254

Gnomad4 NFE exome AF: 0.0170

Gnomad4 OTH exome AF: 0.0116

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000303 AC: 46 AN: 151984 Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23 AN XY: 74316

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000285

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

RPL34: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs1725797981; hg19: chr4-109543133;