Genetic Variant ENST00000639725.1:c.456+1011G>A (chr6-34417358-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000639725.1(RPS10-NUDT3):c.456+1011G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 731,804 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 2 hom. )

Consequence

RPS10-NUDT3
ENST00000639725.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.200

Publications

0 publications found

Variant links:

Genes affected

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-NUDT3 links:

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 Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia
Inheritance: Unknown, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Diamond-Blackfan anemia 9
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

RPS10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 6-34417358-C-T is Benign according to our data. Variant chr6-34417358-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1216886.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00496 (755/152342) while in subpopulation AFR AF = 0.0172 (716/41584). AF 95% confidence interval is 0.0162. There are 3 homozygotes in GnomAd4. There are 374 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000639725.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS10-NUDT3	NM_001202470.3		c.456+1011G>A	intron	N/A	NP_001189399.1	A0A1W2PQS6
RPS10	NM_001014.5	MANE Select	c.*148G>A	downstream_gene	N/A	NP_001005.1	P46783
RPS10	NM_001203245.3		c.*148G>A	downstream_gene	N/A	NP_001190174.1	P46783

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS10-NUDT3	ENST00000639725.1	TSL:5	c.456+1011G>A	intron	N/A	ENSP00000492441.1	A0A1W2PQS6
RPS10-NUDT3	ENST00000639877.1	TSL:5	c.456+1011G>A	intron	N/A	ENSP00000491891.1	A0A1W2PQS6
RPS10-NUDT3	ENST00000605528.2	TSL:5	c.381+1011G>A	intron	N/A	ENSP00000475027.2	S4R435

Frequencies

GnomAD3 genomes

AF:

0.00497

AC:

756

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD4 exome

AF:

0.000554

AC:

321

AN:

579462

Hom.:

AF XY:

0.000422

AC XY:

131

AN XY:

310686

show subpopulations

African (AFR)

AF:

0.0153

AC:

247

AN:

16126

American (AMR)

AF:

0.000793

AC:

AN:

34066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19470

East Asian (EAS)

AF:

0.00

AC:

AN:

32068

South Asian (SAS)

AF:

0.0000490

AC:

AN:

61168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2468

European-Non Finnish (NFE)

AF:

0.0000549

AC:

AN:

346178

Other (OTH)

AF:

0.000798

AC:

AN:

31316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00496

AC:

755

AN:

152342

Hom.:

Cov.:

AF XY:

0.00502

AC XY:

374

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0172

AC:

716

AN:

41584

American (AMR)

AF:

0.00209

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68028

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

124

165

206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00381

Hom.:

Bravo

AF:

0.00542

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.3

(source)

DANN

Benign

0.62

PhyloP100

0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over