chr4-151100479-A-T

Variant names:

• chr4-151100479-A-T
• rs73859998
• NM_001006.5:c.63-6A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001006.5(RPS3A):​c.63-6A>T variant causes a splice region, 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 NM_001006.5 splice_region, intron
• Scores: Splicing: ADA: 0.00004188
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.15
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS3A	NM_001006.5	MANE Select	c.63-6A>T		splice_region intron	N/A	NP_000997.1	P61247
	RPS3A	NM_001267699.2		c.63-6A>T		splice_region intron	N/A	NP_001254628.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS3A	ENST00000274065.9	TSL:1 MANE Select	c.63-6A>T		splice_region intron	N/A	ENSP00000346050.3	P61247
	RPS3A	ENST00000507485.1	TSL:1	n.88-6A>T		splice_region intron	N/A
	RPS3A	ENST00000506126.5	TSL:5	c.-55A>T		5_prime_UTR	Exon 2 of 6	ENSP00000426282.1	D6RAT0

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

GnomAD2 exomes AF: 0.00782 AC: 1958 AN: 250258 AF XY: 0.00589

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 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

African (AFR) AF: 0.100 AC: 3120 AN: 31200

American (AMR) AF: 0.00454 AC: 201 AN: 44298

Ashkenazi Jewish (ASJ) AF: 0.0106 AC: 271 AN: 25452

East Asian (EAS) AF: 0.00 AC: 0 AN: 39142

South Asian (SAS) AF: 0.000405 AC: 34 AN: 83888

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53282

Middle Eastern (MID) AF: 0.0141 AC: 77 AN: 5444

European-Non Finnish (NFE) AF: 0.000441 AC: 448 AN: 1015100

Other (OTH) AF: 0.00765 AC: 436 AN: 57012

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

African (AFR) AF: 0.0971 AC: 4035 AN: 41568

American (AMR) AF: 0.00811 AC: 124 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68028

Other (OTH) AF: 0.0166 AC: 35 AN: 2112

Alfa AF: 0.00375 Hom.: 5

Bravo AF: 0.0312

EpiCase AF: 0.000819

EpiControl AF: 0.00107

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	12
DANN	Benign	0.39
PhyloP100		1.1
Mutation Taster		=75/25	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73859998; hg19: chr4-152021631;