rs147566753

Variant names:

• chr6-34418417-G-A
• rs147566753
• NM_001014.5:c.408C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-34418417-G-A
• chr6-34418417-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001014.5(RPS10):​c.408C>T​(p.Ala136Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,614,098 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A136A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (6 hom.)
• Consequence: RPS10 NM_001014.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -2.43
• Publications: 1 publications found

Genes affected

RPS10 (HGNC:10383): (ribosomal protein S10) 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 S10E family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternate splicing results in multiple transcript variants that encode the same protein. Naturally occurring read-through transcription occurs between this locus and the neighboring locus NUDT3 (nudix (nucleoside diphosphate linked moiety X)-type motif 3).[provided by RefSeq, Feb 2011]

RPS10-NUDT3 (HGNC:49181): (RPS10-NUDT3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring RPS10 (ribosomal protein S10) and NUDT3 (nudix (nucleoside diphosphate linked moiety X)-type motif 3) genes on chromosome 6. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 6-34418417-G-A is Benign according to our data. Variant chr6-34418417-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 356419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.43 with no splicing effect.
• BS2: High AC in GnomAd4 at 277 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014.5. 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
	RPS10	NM_001014.5	MANE Select	c.408C>T	p.Ala136Ala	synonymous	Exon 5 of 6	NP_001005.1	P46783
	RPS10-NUDT3	NM_001202470.3		c.408C>T	p.Ala136Ala	synonymous	Exon 5 of 9	NP_001189399.1	A0A1W2PQS6
	RPS10	NM_001203245.3		c.408C>T	p.Ala136Ala	synonymous	Exon 5 of 6	NP_001190174.1	P46783

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS10	ENST00000648437.1	MANE Select	c.408C>T	p.Ala136Ala	synonymous	Exon 5 of 6	ENSP00000497917.1	P46783
	RPS10-NUDT3	ENST00000639725.1	TSL:5	c.408C>T	p.Ala136Ala	synonymous	Exon 5 of 9	ENSP00000492441.1	A0A1W2PQS6
	RPS10-NUDT3	ENST00000639877.1	TSL:5	c.408C>T	p.Ala136Ala	synonymous	Exon 5 of 9	ENSP00000491891.1	A0A1W2PQS6

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 277 AN: 152100 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00237

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00218 AC: 549 AN: 251448 AF XY: 0.00255

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00115

Gnomad NFE exome AF: 0.00223

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00234 AC: 3422 AN: 1461880 Hom.: 6 Cov.: 31 AF XY: 0.00252 AC XY: 1836 AN XY: 727244

African (AFR) AF: 0.000329 AC: 11 AN: 33480

American (AMR) AF: 0.00134 AC: 60 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00686 AC: 592 AN: 86256

European-Finnish (FIN) AF: 0.00131 AC: 70 AN: 53418

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.00229 AC: 2543 AN: 1112002

Other (OTH) AF: 0.00195 AC: 118 AN: 60396

GnomAD4 genome AF: 0.00182 AC: 277 AN: 152218 Hom.: 2 Cov.: 32 AF XY: 0.00183 AC XY: 136 AN XY: 74420

African (AFR) AF: 0.000722 AC: 30 AN: 41548

American (AMR) AF: 0.00183 AC: 28 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5170

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4820

European-Finnish (FIN) AF: 0.00189 AC: 20 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00237 AC: 161 AN: 68002

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00166 Hom.: 0

Bravo AF: 0.00148

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00267

EpiControl AF: 0.00249

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Diamond-Blackfan anemia (2)
-	-	2	Diamond-Blackfan anemia 9 (2)
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	RPS10-NUDT3-related disorder (1)
-	-	1	RPS10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	1.1
DANN	Benign	0.75
PhyloP100		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs147566753; hg19: chr6-34386194;