Variant 11-125893814-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_031307.4(PUS3):c.1417G>A(p.Val473Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,520 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000082 ( 1 hom. )

Consequence

PUS3
NM_031307.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.524

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.082045734).

BP6

Variant 11-125893814-C-T is Benign according to our data. Variant chr11-125893814-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3390344.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUS3	NM_031307.4 linkuse as main transcript	c.1417G>A	p.Val473Ile	missense_variant	4/4	ENST00000227474.8	NP_112597.4	Q9BZE2
HYLS1	NM_001134793.2 linkuse as main transcript	c.-26+2342C>T		intron_variant		ENST00000425380.7	NP_001128265.1	Q96M11A0A024R3K0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PUS3	ENST00000227474.8 linkuse as main transcript	c.1417G>A	p.Val473Ile	missense_variant	4/4	1	NM_031307.4	ENSP00000227474.3		Q9BZE2
HYLS1	ENST00000425380.7 linkuse as main transcript	c.-26+2342C>T		intron_variant		3	NM_001134793.2	ENSP00000414884.2		Q96M11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251082

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461520

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

PUS3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0079

T;T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.68

.;T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.16

N;N;.

REVEL

Benign

0.072

Sift

Benign

0.38

T;T;.

Sift4G

Benign

0.27

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.14

MutPred

0.13

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;

MVP

0.34

MPC

0.076

ClinPred

0.029

GERP RS

2.0

Varity_R

0.016

gMVP

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over