chr4-107654796-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005443.5(PAPSS1):c.1000C>T(p.Arg334Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000359 in 1,613,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
PAPSS1
NM_005443.5 missense
NM_005443.5 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 4.95
Genes affected
PAPSS1 (HGNC:8603): (3'-phosphoadenosine 5'-phosphosulfate synthase 1) Three-prime-phosphoadenosine 5-prime-phosphosulfate (PAPS) is the sulfate donor cosubstrate for all sulfotransferase (SULT) enzymes (Xu et al., 2000 [PubMed 10679223]). SULTs catalyze the sulfate conjugation of many endogenous and exogenous compounds, including drugs and other xenobiotics. In humans, PAPS is synthesized from adenosine 5-prime triphosphate (ATP) and inorganic sulfate by 2 isoforms, PAPSS1 and PAPSS2 (MIM 603005).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.41362527).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAPSS1 | NM_005443.5 | c.1000C>T | p.Arg334Cys | missense_variant | 8/12 | ENST00000265174.5 | |
PAPSS1 | XM_011532400.3 | c.937C>T | p.Arg313Cys | missense_variant | 8/12 | ||
PAPSS1 | XM_011532401.2 | c.937C>T | p.Arg313Cys | missense_variant | 8/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAPSS1 | ENST00000265174.5 | c.1000C>T | p.Arg334Cys | missense_variant | 8/12 | 1 | NM_005443.5 | P1 | |
PAPSS1 | ENST00000511304.5 | n.692C>T | non_coding_transcript_exon_variant | 6/7 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 151990Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 250954Hom.: 0 AF XY: 0.0000664 AC XY: 9AN XY: 135602
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GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461664Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727148
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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 | Jun 24, 2022 | The c.1000C>T (p.R334C) alteration is located in exon 8 (coding exon 8) of the PAPSS1 gene. This alteration results from a C to T substitution at nucleotide position 1000, causing the arginine (R) at amino acid position 334 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of sheet (P = 0.007);
MVP
MPC
ClinPred
T
GERP RS
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