rs3088241

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_031307.4(PUS3):c.1380G>C(p.Glu460Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,613,484 control chromosomes in the GnomAD database, including 201,370 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 16801 hom., cov: 31)

Exomes 𝑓: 0.50 ( 184569 hom. )

Consequence

PUS3
NM_031307.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00800

Publications

28 publications found

Variant links:

Genes affected

PUS3 (HGNC:25461): (pseudouridine synthase 3) The protein encoded by this gene catalyzes the formation of tRNA pseudouridine from tRNA uridine at position 39 in the anticodon stem and loop of transfer RNAs. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

PUS3 links:

HYLS1 (HGNC:26558): (HYLS1 centriolar and ciliogenesis associated) This gene encodes a protein localized to the cytoplasm. Mutations in this gene are associated with hydrolethalus syndrome. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Oct 2008]

HYLS1 Gene-Disease associations (from GenCC):

hydrolethalus syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
hydrolethalus syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

HYLS1 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 (MetaRNN=9.976661E-5).

BP6

Variant 11-125893851-C-G is Benign according to our data. Variant chr11-125893851-C-G is described in ClinVar as [Benign]. Clinvar id is 1168501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUS3	NM_031307.4 link	c.1380G>C	p.Glu460Asp	missense_variant	Exon 4 of 4	ENST00000227474.8	NP_112597.4	Q9BZE2
HYLS1	NM_001134793.2 link	c.-26+2379C>G		intron_variant	Intron 2 of 2	ENST00000425380.7	NP_001128265.1	Q96M11A0A024R3K0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUS3	ENST00000227474.8 link	c.1380G>C	p.Glu460Asp	missense_variant	Exon 4 of 4	1	NM_031307.4	ENSP00000227474.3		Q9BZE2
HYLS1	ENST00000425380.7 link	c.-26+2379C>G		intron_variant	Intron 2 of 2	3	NM_001134793.2	ENSP00000414884.2		Q96M11

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71155

AN:

151736

Hom.:

16794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.401

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.497

Gnomad FIN

AF:

0.509

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.436

GnomAD2 exomes

AF:

0.492

AC:

123742

AN:

251382

AF XY:

0.496

show subpopulations

Gnomad AFR exome

AF:

0.400

Gnomad AMR exome

AF:

0.457

Gnomad ASJ exome

AF:

0.517

Gnomad EAS exome

AF:

0.536

Gnomad FIN exome

AF:

0.511

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.491

GnomAD4 exome

AF:

0.502

AC:

733023

AN:

1461630

Hom.:

184569

Cov.:

AF XY:

0.502

AC XY:

365269

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.395

AC:

13217

AN:

33472

American (AMR)

AF:

0.456

AC:

20384

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

13604

AN:

26130

East Asian (EAS)

AF:

0.541

AC:

21461

AN:

39696

South Asian (SAS)

AF:

0.518

AC:

44661

AN:

86254

European-Finnish (FIN)

AF:

0.512

AC:

27339

AN:

53418

Middle Eastern (MID)

AF:

0.429

AC:

2475

AN:

5766

European-Non Finnish (NFE)

AF:

0.504

AC:

560128

AN:

1111780

Other (OTH)

AF:

0.493

AC:

29754

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

21273

42547

63820

85094

106367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.469

AC:

71191

AN:

151854

Hom.:

16801

Cov.:

AF XY:

0.470

AC XY:

34862

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.401

AC:

16596

AN:

41398

American (AMR)

AF:

0.454

AC:

6938

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1815

AN:

3464

East Asian (EAS)

AF:

0.531

AC:

2740

AN:

5160

South Asian (SAS)

AF:

0.497

AC:

2384

AN:

4796

European-Finnish (FIN)

AF:

0.509

AC:

5351

AN:

10514

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.499

AC:

33927

AN:

67934

Other (OTH)

AF:

0.441

AC:

930

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1888

3777

5665

7554

9442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.492

Hom.:

13827

Bravo

AF:

0.462

TwinsUK

AF:

0.492

AC:

1826

ALSPAC

AF:

0.517

AC:

1992

ESP6500AA

AF:

0.404

AC:

1779

ESP6500EA

AF:

0.499

AC:

4289

ExAC

AF:

0.493

AC:

59852

Asia WGS

AF:

0.503

AC:

1752

AN:

3478

EpiCase

AF:

0.484

EpiControl

AF:

0.480

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0085

T;T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.60

.;T;T

MetaRNN

Benign

0.00010

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.4

M;M;.

PhyloP100

-0.0080

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.14

N;N;.

REVEL

Benign

0.041

Sift

Benign

0.15

T;T;.

Sift4G

Benign

0.19

T;T;T

Polyphen

0.0030

B;B;.

Vest4

0.032

MutPred

0.092

Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);.;

MPC

0.084

ClinPred

0.0072

GERP RS

-2.1

Varity_R

0.036

gMVP

0.12

Mutation Taster

=100/0

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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rs3088241

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over