chr9-19378522-G-C

Variant names:

• chr9-19378522-G-C
• rs117840373
• NM_001010.3:c.350-8C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001010.3(RPS6):​c.350-8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000806 in 1,610,138 control chromosomes in the GnomAD database, including 17 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 0.00092 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00079 (15 hom.)
• Consequence: RPS6 NM_001010.3 splice_region, intron
• Scores: Splicing: ADA: 0.0003043
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.393
• Publications: 1 publications found

Genes affected

RPS6 (HGNC:10429): (ribosomal protein S6) 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 cytoplasmic ribosomal protein that is a component of the 40S subunit. The protein belongs to the S6E family of ribosomal proteins. It is the major substrate of protein kinases in the ribosome, with subsets of five C-terminal serine residues phosphorylated by different protein kinases. Phosphorylation is induced by a wide range of stimuli, including growth factors, tumor-promoting agents, and mitogens. Dephosphorylation occurs at growth arrest. The protein may contribute to the control of cell growth and proliferation through the selective translation of particular classes of mRNA. 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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-19378522-G-C is Benign according to our data. Variant chr9-19378522-G-C is described in ClinVar as Benign. ClinVar VariationId is 708362.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000919 (140/152258) while in subpopulation EAS AF = 0.0204 (106/5188). AF 95% confidence interval is 0.0173. There are 2 homozygotes in GnomAd4. There are 85 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 140 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010.3. 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
	RPS6	NM_001010.3	MANE Select	c.350-8C>G		splice_region intron	N/A	NP_001001.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6	ENST00000380394.9	TSL:1 MANE Select	c.350-8C>G		splice_region intron	N/A	ENSP00000369757.4	P62753
	RPS6	ENST00000380384.5	TSL:1	c.257-8C>G		splice_region intron	N/A	ENSP00000369745.1	A2A3R5
	RPS6	ENST00000889073.1		c.374-8C>G		splice_region intron	N/A	ENSP00000559132.1

Frequencies

GnomAD3 genomes AF: 0.000920 AC: 140 AN: 152140 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00212 AC: 521 AN: 245520 AF XY: 0.00202

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00335

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.0195

Gnomad FIN exome AF: 0.000882

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.000504

GnomAD4 exome AF: 0.000794 AC: 1158 AN: 1457880 Hom.: 15 Cov.: 31 AF XY: 0.000794 AC XY: 576 AN XY: 725130

African (AFR) AF: 0.00 AC: 0 AN: 33126

American (AMR) AF: 0.00298 AC: 130 AN: 43586

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25948

East Asian (EAS) AF: 0.0203 AC: 805 AN: 39670

South Asian (SAS) AF: 0.000797 AC: 68 AN: 85298

European-Finnish (FIN) AF: 0.000862 AC: 46 AN: 53358

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5734

European-Non Finnish (NFE) AF: 0.0000513 AC: 57 AN: 1110944

Other (OTH) AF: 0.000781 AC: 47 AN: 60216

GnomAD4 genome AF: 0.000919 AC: 140 AN: 152258 Hom.: 2 Cov.: 33 AF XY: 0.00114 AC XY: 85 AN XY: 74462

African (AFR) AF: 0.00 AC: 0 AN: 41542

American (AMR) AF: 0.000785 AC: 12 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0204 AC: 106 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.000848 AC: 9 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68014

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000405 Hom.: 0

Bravo AF: 0.00134

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.43
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00030
dbscSNV1_RF	Benign	0.096
SpliceAI score (max)		0.010		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: rs117840373; hg19: chr9-19378520;