14-49583678-GAAAA-GAAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_001032.5(RPS29):c.163-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,085,416 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.022 ( 0 hom. )

Consequence

RPS29
NM_001032.5 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.536

Publications

1 publications found

Variant links:

Genes affected

RPS29 (HGNC:10419): (ribosomal protein S29) 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 and a member of the S14P family of ribosomal proteins. The protein, which contains a C2-C2 zinc finger-like domain that can bind to zinc, can enhance the tumor suppressor activity of Ras-related protein 1A (KREV1). 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2013]

RPS29 Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia 13
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
Diamond-Blackfan anemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RPS29 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP6

Variant 14-49583678-GA-G is Benign according to our data. Variant chr14-49583678-GA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1293204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS29	NM_001032.5	MANE Select	c.163-4delT	splice_region intron	N/A	NP_001023.1	P62273-1
RPS29	NM_001030001.4		c.162+2271delT	intron	N/A	NP_001025172.1	P62273-2
RPS29	NM_001351375.2		c.154-4delT	splice_region intron	N/A	NP_001338304.1	A0A087WTT6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS29	ENST00000245458.11	TSL:1 MANE Select	c.163-4delT	splice_region intron	N/A	ENSP00000245458.7	P62273-1
RPS29	ENST00000396020.7	TSL:1	c.162+2271delT	intron	N/A	ENSP00000379339.3	P62273-2
RPS29	ENST00000556230.2	TSL:1	c.163-4delT	splice_region intron	N/A	ENSP00000495033.1	P62273-1

Frequencies

GnomAD3 genomes

AF:

0.000239

AC:

AN:

138254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000291

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000677

Gnomad FIN

AF:

0.00127

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000173

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0466

AC:

4120

AN:

88432

AF XY:

0.0457

show subpopulations

Gnomad AFR exome

AF:

0.0388

Gnomad AMR exome

AF:

0.0657

Gnomad ASJ exome

AF:

0.0628

Gnomad EAS exome

AF:

0.0496

Gnomad FIN exome

AF:

0.0221

Gnomad NFE exome

AF:

0.0464

Gnomad OTH exome

AF:

0.0471

GnomAD4 exome

AF:

0.0217

AC:

20593

AN:

947108

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

10096

AN XY:

472028

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0245

AC:

510

AN:

20798

American (AMR)

AF:

0.0332

AC:

862

AN:

25944

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

405

AN:

16340

East Asian (EAS)

AF:

0.0209

AC:

504

AN:

24130

South Asian (SAS)

AF:

0.0220

AC:

1173

AN:

53212

European-Finnish (FIN)

AF:

0.0172

AC:

599

AN:

34750

Middle Eastern (MID)

AF:

0.0161

AC:

AN:

4040

European-Non Finnish (NFE)

AF:

0.0214

AC:

15600

AN:

729586

Other (OTH)

AF:

0.0228

AC:

875

AN:

38308

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

2896

5792

8688

11584

14480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

598

1196

1794

2392

2990

<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:

0.000239

AC:

AN:

138308

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

AN XY:

66754

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000159

AC:

AN:

37732

American (AMR)

AF:

0.000290

AC:

AN:

13772

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3278

East Asian (EAS)

AF:

0.00

AC:

AN:

4804

South Asian (SAS)

AF:

0.000453

AC:

AN:

4414

European-Finnish (FIN)

AF:

0.00127

AC:

AN:

7874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.000173

AC:

AN:

63404

Other (OTH)

AF:

0.00

AC:

AN:

1888

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000014766), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.327

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0250

Hom.:

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Diamond-Blackfan anemia 13 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.54

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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