4-151102899-A-G

Variant names:

• chr4-151102899-A-G
• rs758026158
• NM_001006.5:c.383A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001006.5(RPS3A):​c.383A>G​(p.Lys128Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,660 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: RPS3A NM_001006.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.48
• Publications: 0 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]

SH3D19 (HGNC:30418): (SH3 domain containing 19) This gene encodes a multiple SH3 domain-containing protein, which interacts with other proteins, such as EBP and members of ADAM family, via the SH3 domains. This protein may be involved in suppression of Ras-induced cellular transformation and Ras-mediated activation of ELK1 by EBP, and regulation of ADAM proteins in the signaling of EGFR-ligand shedding. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 8 AD gene.

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.383A>G	p.Lys128Arg	missense	Exon 4 of 6	NP_000997.1	P61247
	RPS3A	NM_001267699.2		c.*18A>G		3_prime_UTR	Exon 3 of 3	NP_001254628.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS3A	ENST00000274065.9	TSL:1 MANE Select	c.383A>G	p.Lys128Arg	missense	Exon 4 of 6	ENSP00000346050.3	P61247
	RPS3A	ENST00000507485.1	TSL:1	n.220A>G		non_coding_transcript_exon	Exon 3 of 3
	RPS3A	ENST00000913221.1		c.383A>G	p.Lys128Arg	missense	Exon 4 of 6	ENSP00000583280.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248548 AF XY: 0.00000742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000267

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1459660 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4 AN XY: 726116

African (AFR) AF: 0.0000299 AC: 1 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5296

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110862

Other (OTH) AF: 0.0000498 AC: 3 AN: 60242

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	0.086
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.5
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.16
Sift	Benign	0.070	T
Sift4G	Benign	0.11	T
Polyphen		0.14	B
Vest4		0.53
MutPred		0.58		Loss of ubiquitination at K128 (P = 0.0297)
MVP		0.67
MPC		0.91
ClinPred		0.57	D
GERP RS		3.6
Varity_R		0.19
gMVP		0.78
Mutation Taster		=51/49	polymorphism

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

Other links and lift over

dbSNP: rs758026158; hg19: chr4-152024051;