rs201997946

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031307.4(PUS3):​c.1361A>T​(p.Asn454Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N454S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PUS3
NM_031307.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.269
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]
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]

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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=0.06635091).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PUS3NM_031307.4 linkc.1361A>T p.Asn454Ile missense_variant Exon 4 of 4 ENST00000227474.8 NP_112597.4 Q9BZE2
HYLS1NM_001134793.2 linkc.-26+2398T>A 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
PUS3ENST00000227474.8 linkc.1361A>T p.Asn454Ile missense_variant Exon 4 of 4 1 NM_031307.4 ENSP00000227474.3 Q9BZE2
HYLS1ENST00000425380.7 linkc.-26+2398T>A intron_variant Intron 2 of 2 3 NM_001134793.2 ENSP00000414884.2 Q96M11

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
10
DANN
Benign
0.96
DEOGEN2
Benign
0.0089
T;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.70
.;T;T
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.066
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
M;M;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.4
N;N;.
REVEL
Benign
0.049
Sift
Benign
0.031
D;D;.
Sift4G
Benign
0.19
T;T;T
Polyphen
0.12
B;B;.
Vest4
0.23
MutPred
0.13
Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);.;
MVP
0.47
MPC
0.12
ClinPred
0.057
T
GERP RS
-2.4
Varity_R
0.078
gMVP
0.24

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.

Other links and lift over

dbSNP: rs201997946; hg19: chr11-125763765; API