ENST00000937795.1:c.-384C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000937795.1(RPS25):c.-384C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,088,050 control chromosomes in the GnomAD database, including 53,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 14113 hom., cov: 33)

Exomes 𝑓: 0.27 ( 39554 hom. )

Consequence

RPS25
ENST00000937795.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.22

Publications

14 publications found

Variant links:

Genes affected

RPS25 (HGNC:10413): (ribosomal protein S25) 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 S25E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS25 links:

TRAPPC4 (HGNC:19943): (trafficking protein particle complex subunit 4) Involved in autophagy and endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

TRAPPC4 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen
syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRAPPC4 links:

ENSG00000300421 (HGNC:):

ENSG00000300421 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 11-119018668-G-A is Benign according to our data. Variant chr11-119018668-G-A is described in ClinVar as Benign. ClinVar VariationId is 1240845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000937795.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRAPPC4	NM_016146.6	MANE Select	c.-128G>A	upstream_gene	N/A	NP_057230.1	Q9Y296-1
TRAPPC4	NM_001318488.2		c.-128G>A	upstream_gene	N/A	NP_001305417.1	J3KP27
TRAPPC4	NM_001318490.2		c.-128G>A	upstream_gene	N/A	NP_001305419.1	E9PQE8

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
RPS25	ENST00000937795.1	c.-384C>T	5_prime_UTR	Exon 1 of 5	ENSP00000607854.1
RPS25	ENST00000942362.1	c.-384C>T	5_prime_UTR	Exon 1 of 5	ENSP00000612421.1
RPS25	ENST00000937796.1	c.-384C>T	5_prime_UTR	Exon 1 of 5	ENSP00000607855.1

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58414

AN:

151732

Hom.:

14064

Cov.:

show subpopulations

Gnomad AFR

AF:

0.693

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.347

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.341

GnomAD4 exome

AF:

0.272

AC:

254646

AN:

936200

Hom.:

39554

Cov.:

AF XY:

0.275

AC XY:

130833

AN XY:

476148

show subpopulations

African (AFR)

AF:

0.703

AC:

15959

AN:

22686

American (AMR)

AF:

0.209

AC:

7696

AN:

36748

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

3908

AN:

18726

East Asian (EAS)

AF:

0.155

AC:

5748

AN:

37054

South Asian (SAS)

AF:

0.357

AC:

23734

AN:

66536

European-Finnish (FIN)

AF:

0.307

AC:

12945

AN:

42214

Middle Eastern (MID)

AF:

0.252

AC:

861

AN:

3420

European-Non Finnish (NFE)

AF:

0.257

AC:

171396

AN:

666594

Other (OTH)

AF:

0.294

AC:

12399

AN:

42222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

9160

18320

27480

36640

45800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4722

9444

14166

18888

23610

<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:

0.385

AC:

58517

AN:

151850

Hom.:

14113

Cov.:

AF XY:

0.384

AC XY:

28479

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.693

AC:

28660

AN:

41354

American (AMR)

AF:

0.279

AC:

4270

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

691

AN:

3464

East Asian (EAS)

AF:

0.149

AC:

771

AN:

5172

South Asian (SAS)

AF:

0.373

AC:

1802

AN:

4832

European-Finnish (FIN)

AF:

0.324

AC:

3425

AN:

10566

Middle Eastern (MID)

AF:

0.349

AC:

102

AN:

292

European-Non Finnish (NFE)

AF:

0.264

AC:

17911

AN:

67874

Other (OTH)

AF:

0.343

AC:

721

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1599

3198

4798

6397

7996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.305

Hom.:

1693

Bravo

AF:

0.394

Asia WGS

AF:

0.298

AC:

1039

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.75

(source)

DANN

Benign

0.82

PhyloP100

-1.2

PromoterAI

0.0020

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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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