rs147863199

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-34424760-C-A
• chr6-34424760-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001014.5(RPS10):​c.231G>T​(p.Gln77His) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q77Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RPS10 NM_001014.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.98
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.886

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS10	NM_001014.5	c.231G>T	p.Gln77His	missense_variant	Exon 3 of 6	ENST00000648437.1	NP_001005.1
RPS10-NUDT3	NM_001202470.3	c.231G>T	p.Gln77His	missense_variant	Exon 3 of 9		NP_001189399.1
RPS10	NM_001203245.3	c.231G>T	p.Gln77His	missense_variant	Exon 3 of 6		NP_001190174.1
RPS10	NM_001204091.2	c.231G>T	p.Gln77His	missense_variant	Exon 3 of 6		NP_001191020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS10	ENST00000648437.1	c.231G>T	p.Gln77His	missense_variant	Exon 3 of 6		NM_001014.5	ENSP00000497917.1
RPS10-NUDT3	ENST00000639725.1	c.231G>T	p.Gln77His	missense_variant	Exon 3 of 9	5		ENSP00000492441.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461814 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111992

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	.;.;.;T;T;T;.;.;T;T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.65	.;T;T;.;.;.;T;T;.;T;T
M_CAP	Pathogenic	0.44	D
MetaRNN	Pathogenic	0.89	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Pathogenic	3.1	.;.;.;M;M;M;.;.;M;M;.
PhyloP100		5.0
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.0	.;.;.;.;.;.;D;.;.;D;.
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0010	.;.;.;.;.;.;D;.;.;D;.
Sift4G	Uncertain	0.0030	.;.;.;.;.;D;D;.;.;D;.
Polyphen		1.0	.;.;.;D;D;D;.;.;D;D;.
Vest4		0.86, 0.88
MutPred		0.54		Loss of catalytic residue at Q77 (P = 0.0411);Loss of catalytic residue at Q77 (P = 0.0411);Loss of catalytic residue at Q77 (P = 0.0411);Loss of catalytic residue at Q77 (P = 0.0411);Loss of catalytic residue at Q77 (P = 0.0411);Loss of catalytic residue at Q77 (P = 0.0411);Loss of catalytic residue at Q77 (P = 0.0411);Loss of catalytic residue at Q77 (P = 0.0411);Loss of catalytic residue at Q77 (P = 0.0411);Loss of catalytic residue at Q77 (P = 0.0411);Loss of catalytic residue at Q77 (P = 0.0411);
MVP		0.68
MPC		1.4
ClinPred		1.0	D
GERP RS		4.3
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.79
gMVP		0.58
Mutation Taster		=5/95	disease causing

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;