chr22-39317633-C-CA

Position:

• chr22-39317633-C-CA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000967.4(RPL3):​c.197-5_197-4insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,551,016 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (1 hom.)
• Consequence: RPL3 NM_000967.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.858

Genes affected

RPL3 (HGNC:10332): (ribosomal protein L3) Ribosomes, the complexes 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 L3P family of ribosomal proteins and it is located in the cytoplasm. The protein can bind to the HIV-1 TAR mRNA, and it has been suggested that the protein contributes to tat-mediated transactivation. This gene is co-transcribed with several small nucleolar RNA genes, which are located in several of this gene's introns. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 22-39317633-C-CA is Benign according to our data. Variant chr22-39317633-C-CA is described in ClinVar as [Benign]. Clinvar id is 781529.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 57 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL3	NM_000967.4	c.197-5_197-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000216146.9
RPL3	NM_001033853.2	c.197-5_197-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL3	ENST00000216146.9	c.197-5_197-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000967.4	P1

Frequencies

GnomAD3 genomes AF: 0.000379 AC: 57 AN: 150228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00172

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000970

Gnomad SAS AF: 0.000844

Gnomad FIN AF: 0.000197

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000178

Gnomad OTH AF: 0.00145

GnomAD4 exome AF: 0.000478 AC: 669 AN: 1400678 Hom.: 1 Cov.: 31 AF XY: 0.000518 AC XY: 361 AN XY: 696620

Gnomad4 AFR exome AF: 0.000322

Gnomad4 AMR exome AF: 0.00163

Gnomad4 ASJ exome AF: 0.000368

Gnomad4 EAS exome AF: 0.00134

Gnomad4 SAS exome AF: 0.00110

Gnomad4 FIN exome AF: 0.000291

Gnomad4 NFE exome AF: 0.000373

Gnomad4 OTH exome AF: 0.000524

GnomAD4 genome AF: 0.000379 AC: 57 AN: 150338 Hom.: 0 Cov.: 32 AF XY: 0.000423 AC XY: 31 AN XY: 73372

Gnomad4 AFR AF: 0.000122

Gnomad4 AMR AF: 0.00172

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000972

Gnomad4 SAS AF: 0.000845

Gnomad4 FIN AF: 0.000197

Gnomad4 NFE AF: 0.000178

Gnomad4 OTH AF: 0.00143

Bravo AF: 0.000348

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs201453499; hg19: chr22-39713638;