chr11-126209627-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_032795.3(RPUSD4):c.451C>T(p.Arg151Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000663 in 1,614,192 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00029 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000043 ( 2 hom. )
Consequence
RPUSD4
NM_032795.3 missense
NM_032795.3 missense
Scores
8
9
2
Clinical Significance
Conservation
PhyloP100: 4.91
Genes affected
RPUSD4 (HGNC:25898): (RNA pseudouridine synthase D4) Enables mitochondrial ribosomal large subunit rRNA binding activity; pseudouridine synthase activity; and tRNA binding activity. Involved in mitochondrial tRNA pseudouridine synthesis and positive regulation of mitochondrial translation. Located in mitochondrion; nucleoplasm; and ribonucleoprotein granule. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPUSD4 | NM_032795.3 | c.451C>T | p.Arg151Trp | missense_variant | 3/7 | ENST00000298317.9 | |
RPUSD4 | NM_001363516.2 | c.451C>T | p.Arg151Trp | missense_variant | 3/7 | ||
RPUSD4 | NM_001144827.2 | c.451C>T | p.Arg151Trp | missense_variant | 3/7 | ||
RPUSD4 | XM_011543039.3 | c.-156C>T | 5_prime_UTR_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPUSD4 | ENST00000298317.9 | c.451C>T | p.Arg151Trp | missense_variant | 3/7 | 1 | NM_032795.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000283 AC: 43AN: 152198Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000115 AC: 29AN: 251476Hom.: 1 AF XY: 0.000110 AC XY: 15AN XY: 135918
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GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461876Hom.: 2 Cov.: 31 AF XY: 0.0000454 AC XY: 33AN XY: 727242
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GnomAD4 genome AF: 0.000289 AC: 44AN: 152316Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74470
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 08, 2024 | The c.451C>T (p.R151W) alteration is located in exon 3 (coding exon 3) of the RPUSD4 gene. This alteration results from a C to T substitution at nucleotide position 451, causing the arginine (R) at amino acid position 151 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at