rs147863199

Variant names:

• chr6-34424760-C-T
• rs147863199
• NM_001014.5:c.231G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-34424760-C-T
• chr6-34424760-C-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.231G>A​(p.Gln77Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.00204 in 1,614,136 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (7 hom.)
• Consequence: RPS10 NM_001014.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.98
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 6-34424760-C-T is Benign according to our data. Variant chr6-34424760-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 238211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 187 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.231G>A	p.Gln77Gln	synonymous	Exon 3 of 6	NP_001005.1	P46783
	RPS10-NUDT3	NM_001202470.3		c.231G>A	p.Gln77Gln	synonymous	Exon 3 of 9	NP_001189399.1	A0A1W2PQS6
	RPS10	NM_001203245.3		c.231G>A	p.Gln77Gln	synonymous	Exon 3 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.231G>A	p.Gln77Gln	synonymous	Exon 3 of 6	ENSP00000497917.1	P46783
	RPS10-NUDT3	ENST00000639725.1	TSL:5	c.231G>A	p.Gln77Gln	synonymous	Exon 3 of 9	ENSP00000492441.1	A0A1W2PQS6
	RPS10-NUDT3	ENST00000639877.1	TSL:5	c.231G>A	p.Gln77Gln	synonymous	Exon 3 of 9	ENSP00000491891.1	A0A1W2PQS6

Frequencies

GnomAD3 genomes AF: 0.00124 AC: 188 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00188

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00167 AC: 418 AN: 250462 AF XY: 0.00166

Gnomad AFR exome AF: 0.000439

Gnomad AMR exome AF: 0.000666

Gnomad ASJ exome AF: 0.00368

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000556

Gnomad NFE exome AF: 0.00268

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00213 AC: 3109 AN: 1461814 Hom.: 7 Cov.: 31 AF XY: 0.00211 AC XY: 1535 AN XY: 727212

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.000693 AC: 31 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00341 AC: 89 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000788 AC: 68 AN: 86252

European-Finnish (FIN) AF: 0.000806 AC: 43 AN: 53374

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00247 AC: 2743 AN: 1111992

Other (OTH) AF: 0.00210 AC: 127 AN: 60392

GnomAD4 genome AF: 0.00123 AC: 187 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.00102 AC XY: 76 AN XY: 74482

African (AFR) AF: 0.000553 AC: 23 AN: 41574

American (AMR) AF: 0.000523 AC: 8 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00188 AC: 128 AN: 68040

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00205 Hom.: 0

Bravo AF: 0.00116

EpiCase AF: 0.00169

EpiControl AF: 0.00154

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 specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	13
DANN	Benign	0.95
PhyloP100		5.0
PromoterAI		-0.017	Neutral
Mutation Taster		=83/17	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: rs147863199; hg19: chr6-34392537;