rs146246722

Variant names:

• chr6-34425216-C-T
• rs146246722
• NM_001014.5:c.6G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001014.5(RPS10):​c.6G>A​(p.Leu2Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000491 in 1,608,702 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (3 hom.)
• Consequence: RPS10 NM_001014.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.95
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 6-34425216-C-T is Benign according to our data. Variant chr6-34425216-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 356423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 102 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.6G>A	p.Leu2Leu	synonymous	Exon 2 of 6	NP_001005.1	P46783
	RPS10-NUDT3	NM_001202470.3		c.6G>A	p.Leu2Leu	synonymous	Exon 2 of 9	NP_001189399.1	A0A1W2PQS6
	RPS10	NM_001203245.3		c.6G>A	p.Leu2Leu	synonymous	Exon 2 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.6G>A	p.Leu2Leu	synonymous	Exon 2 of 6	ENSP00000497917.1	P46783
	RPS10-NUDT3	ENST00000639725.1	TSL:5	c.6G>A	p.Leu2Leu	synonymous	Exon 2 of 9	ENSP00000492441.1	A0A1W2PQS6
	RPS10-NUDT3	ENST00000639877.1	TSL:5	c.6G>A	p.Leu2Leu	synonymous	Exon 2 of 9	ENSP00000491891.1	A0A1W2PQS6

Frequencies

GnomAD3 genomes AF: 0.000670 AC: 102 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000851 AC: 202 AN: 237388 AF XY: 0.000905

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00475

Gnomad FIN exome AF: 0.00325

Gnomad NFE exome AF: 0.000415

Gnomad OTH exome AF: 0.000508

GnomAD4 exome AF: 0.000472 AC: 688 AN: 1456440 Hom.: 3 Cov.: 32 AF XY: 0.000478 AC XY: 346 AN XY: 724054

African (AFR) AF: 0.0000299 AC: 1 AN: 33422

American (AMR) AF: 0.0000229 AC: 1 AN: 43736

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 26000

East Asian (EAS) AF: 0.00464 AC: 184 AN: 39654

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85578

European-Finnish (FIN) AF: 0.00410 AC: 215 AN: 52392

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.000217 AC: 241 AN: 1109620

Other (OTH) AF: 0.000581 AC: 35 AN: 60272

GnomAD4 genome AF: 0.000670 AC: 102 AN: 152262 Hom.: 0 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74448

African (AFR) AF: 0.0000241 AC: 1 AN: 41556

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00301 AC: 32 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000617 AC: 42 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000585 Hom.: 0

Bravo AF: 0.000223

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.73
PhyloP100		4.9
PromoterAI		0.013	Neutral
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs146246722; hg19: chr6-34392993; COSMIC: COSV58242277; COSMIC: COSV58242277;