chr6-34425219-C-T

Position:

• chr6-34425219-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001014.5(RPS10):​c.3G>A​(p.Met1?) variant causes a start lost, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RPS10 NM_001014.5 start_lost, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.88

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]

RPS10 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-34425219-C-T is Pathogenic according to our data. Variant chr6-34425219-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 6185.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-34425219-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS10	NM_001014.5	c.3G>A	p.Met1?	start_lost, splice_region_variant	2/6	ENST00000648437.1	NP_001005.1
RPS10-NUDT3	NM_001202470.3	c.3G>A	p.Met1?	start_lost, splice_region_variant	2/9		NP_001189399.1
RPS10	NM_001203245.3	c.3G>A	p.Met1?	start_lost, splice_region_variant	2/6		NP_001190174.1
RPS10	NM_001204091.2	c.3G>A	p.Met1?	start_lost, splice_region_variant	2/6		NP_001191020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS10	ENST00000648437.1	c.3G>A	p.Met1?	start_lost, splice_region_variant	2/6		NM_001014.5	ENSP00000497917.1
RPS10-NUDT3	ENST00000639725.1	c.3G>A	p.Met1?	start_lost, splice_region_variant	2/9	5		ENSP00000492441.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Diamond-Blackfan anemia 9 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 12, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	.;.;.;T;T;T;.;.;T;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	.;D;D;.;.;.;D;D;.;D;D
M_CAP	Pathogenic	0.66	D
MetaRNN	Pathogenic	0.99	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.42	T
PROVEAN	Uncertain	-3.5	.;.;.;.;.;.;D;.;.;D;.
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0010	.;.;.;.;.;.;D;.;.;D;.
Sift4G	Uncertain	0.0020	.;.;.;.;.;D;D;.;.;D;.
Polyphen		0.041	.;.;.;B;B;B;.;.;B;B;.
Vest4		0.95, 0.95
MutPred		0.90		Loss of MoRF binding (P = 0.0738);Loss of MoRF binding (P = 0.0738);Loss of MoRF binding (P = 0.0738);Loss of MoRF binding (P = 0.0738);Loss of MoRF binding (P = 0.0738);Loss of MoRF binding (P = 0.0738);Loss of MoRF binding (P = 0.0738);Loss of MoRF binding (P = 0.0738);Loss of MoRF binding (P = 0.0738);Loss of MoRF binding (P = 0.0738);Loss of MoRF binding (P = 0.0738);
MVP		0.77
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.95
gMVP		0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs267607021; hg19: chr6-34392996;