rs116500841

Variant names:

• chr6-34417721-A-G
• rs116500841
• NM_001014.5:c.457-174T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-34417721-A-G
• chr6-34417721-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001014.5(RPS10):​c.457-174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 731,970 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0084 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (23 hom.)
• Consequence: RPS10 NM_001014.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.182
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-34417721-A-G is Benign according to our data. Variant chr6-34417721-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1213487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00837 (1274/152298) while in subpopulation AFR AF = 0.0238 (991/41572). AF 95% confidence interval is 0.0226. There are 11 homozygotes in GnomAd4. There are 599 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1274 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.457-174T>C		intron	N/A	NP_001005.1	P46783
	RPS10-NUDT3	NM_001202470.3		c.456+648T>C		intron	N/A	NP_001189399.1	A0A1W2PQS6
	RPS10	NM_001203245.3		c.457-174T>C		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.457-174T>C		intron	N/A	ENSP00000497917.1	P46783
	RPS10-NUDT3	ENST00000639725.1	TSL:5	c.456+648T>C		intron	N/A	ENSP00000492441.1	A0A1W2PQS6
	RPS10	ENST00000644700.1		c.*462T>C		3_prime_UTR	Exon 5 of 5	ENSP00000495142.1	A0A2R8YFH6

Frequencies

GnomAD3 genomes AF: 0.00836 AC: 1272 AN: 152180 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.00280 AC: 1625 AN: 579672 Hom.: 23 Cov.: 6 AF XY: 0.00254 AC XY: 792 AN XY: 311222

African (AFR) AF: 0.0235 AC: 375 AN: 15930

American (AMR) AF: 0.00651 AC: 221 AN: 33954

Ashkenazi Jewish (ASJ) AF: 0.0227 AC: 446 AN: 19642

East Asian (EAS) AF: 0.00 AC: 0 AN: 32116

South Asian (SAS) AF: 0.0000481 AC: 3 AN: 62394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48724

Middle Eastern (MID) AF: 0.00587 AC: 24 AN: 4088

European-Non Finnish (NFE) AF: 0.00119 AC: 395 AN: 331768

Other (OTH) AF: 0.00518 AC: 161 AN: 31056

GnomAD4 genome AF: 0.00837 AC: 1274 AN: 152298 Hom.: 11 Cov.: 32 AF XY: 0.00804 AC XY: 599 AN XY: 74462

African (AFR) AF: 0.0238 AC: 991 AN: 41572

American (AMR) AF: 0.00576 AC: 88 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00126 AC: 86 AN: 68022

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.000925 Hom.: 0

Bravo AF: 0.00967

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.62
PhyloP100		0.18
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: rs116500841; hg19: chr6-34385498;