chr4-151100479-A-T

Position:

• chr4-151100479-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000274065.9(RPS3A):​c.63-6A>T 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 0.00587 in 1,507,156 control chromosomes in the GnomAD database, including 363 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (196 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (167 hom.)
• Consequence: RPS3A ENST00000274065.9 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004188
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.15

Genes affected

RPS3A (HGNC:10421): (ribosomal protein S3A) 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 40S subunit. The protein belongs to the S3AE family of ribosomal proteins. It is located in the cytoplasm. Disruption of the gene encoding rat ribosomal protein S3a, also named v-fos transformation effector protein, in v-fos-transformed rat cells results in reversion of the transformed phenotype. This gene is co-transcribed with the U73A and U73B small nucleolar RNA genes, which are located in its fourth and third introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 4-151100479-A-T is Benign according to our data. Variant chr4-151100479-A-T is described in ClinVar as [Benign]. Clinvar id is 778160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS3A	NM_001006.5	c.63-6A>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000274065.9	NP_000997.1
RPS3A	NM_001267699.2	c.63-6A>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001254628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS3A	ENST00000274065.9	c.63-6A>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001006.5	ENSP00000346050	P1

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4242 AN: 152220 Hom.: 196 Cov.: 33

Gnomad AFR AF: 0.0968

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00812

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00782 AC: 1958 AN: 250258 Hom.: 81 AF XY: 0.00589 AC XY: 797 AN XY: 135312

Gnomad AFR exome AF: 0.0968

Gnomad AMR exome AF: 0.00435

Gnomad ASJ exome AF: 0.0134

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000461

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000617

Gnomad OTH exome AF: 0.00394

GnomAD4 exome AF: 0.00339 AC: 4588 AN: 1354818 Hom.: 167 Cov.: 20 AF XY: 0.00306 AC XY: 2083 AN XY: 680562

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.00454

Gnomad4 ASJ exome AF: 0.0106

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000405

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000441

Gnomad4 OTH exome AF: 0.00765

GnomAD4 genome AF: 0.0280 AC: 4265 AN: 152338 Hom.: 196 Cov.: 33 AF XY: 0.0267 AC XY: 1986 AN XY: 74492

Gnomad4 AFR AF: 0.0971

Gnomad4 AMR AF: 0.00811

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.00375 Hom.: 5

Bravo AF: 0.0312

EpiCase AF: 0.000819

EpiControl AF: 0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	12
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000042
dbscSNV1_RF	Benign	0.052
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: rs73859998; hg19: chr4-152021631;