NM_001014.5:c.456+226dupA

Variant names:

• chr6-34418142-G-GT
• rs201724991
• NM_001014.5:c.456+226dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001014.5(RPS10):​c.456+226dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,456,772 control chromosomes in the GnomAD database, including 104 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (52 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (52 hom.)
• Consequence: RPS10 NM_001014.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0300
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 6-34418142-G-GT is Benign according to our data. Variant chr6-34418142-G-GT is described in ClinVar as Benign. ClinVar VariationId is 1228151.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

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.456+226dupA		intron	N/A	NP_001005.1	P46783
	RPS10-NUDT3	NM_001202470.3		c.456+226dupA		intron	N/A	NP_001189399.1	A0A1W2PQS6
	RPS10	NM_001203245.3		c.456+226dupA		intron	N/A	NP_001190174.1	P46783

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS10	ENST00000648437.1	MANE Select	c.456+226dupA		intron	N/A	ENSP00000497917.1	P46783
	RPS10-NUDT3	ENST00000639725.1	TSL:5	c.456+226dupA		intron	N/A	ENSP00000492441.1	A0A1W2PQS6
	RPS10	ENST00000644700.1		c.*40dupA		3_prime_UTR	Exon 5 of 5	ENSP00000495142.1	A0A2R8YFH6

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2358 AN: 152122 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00799

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.00190 AC: 2476 AN: 1304532 Hom.: 52 Cov.: 28 AF XY: 0.00181 AC XY: 1150 AN XY: 635594

African (AFR) AF: 0.0527 AC: 1504 AN: 28526

American (AMR) AF: 0.00647 AC: 148 AN: 22876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19704

East Asian (EAS) AF: 0.00 AC: 0 AN: 35108

South Asian (SAS) AF: 0.000317 AC: 20 AN: 63138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42312

Middle Eastern (MID) AF: 0.00577 AC: 21 AN: 3642

European-Non Finnish (NFE) AF: 0.000485 AC: 502 AN: 1035220

Other (OTH) AF: 0.00520 AC: 281 AN: 54006

GnomAD4 genome AF: 0.0155 AC: 2360 AN: 152240 Hom.: 52 Cov.: 32 AF XY: 0.0146 AC XY: 1086 AN XY: 74428

African (AFR) AF: 0.0516 AC: 2142 AN: 41530

American (AMR) AF: 0.00798 AC: 122 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000794 AC: 54 AN: 68028

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0179

Asia WGS AF: 0.00202 AC: 7 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
PhyloP100		0.030
Mutation Taster		=100/0	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: rs201724991; hg19: chr6-34385919;