rs17124941
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_001015880.2(PAPSS2):āc.276T>Cā(p.Ser92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,609,440 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.0033 ( 8 hom., cov: 28)
Exomes š: 0.0033 ( 103 hom. )
Consequence
PAPSS2
NM_001015880.2 synonymous
NM_001015880.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.249
Genes affected
PAPSS2 (HGNC:8604): (3'-phosphoadenosine 5'-phosphosulfate synthase 2) Sulfation is a common modification of endogenous (lipids, proteins, and carbohydrates) and exogenous (xenobiotics and drugs) compounds. In mammals, the sulfate source is 3'-phosphoadenosine 5'-phosphosulfate (PAPS), created from ATP and inorganic sulfate. Two different tissue isoforms encoded by different genes synthesize PAPS. This gene encodes one of the two PAPS synthetases. Defects in this gene cause the Pakistani type of spondyloepimetaphyseal dysplasia. Two alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 10-87713205-T-C is Benign according to our data. Variant chr10-87713205-T-C is described in ClinVar as [Benign]. Clinvar id is 537718.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.249 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00331 (494/149136) while in subpopulation EAS AF= 0.0389 (193/4960). AF 95% confidence interval is 0.0344. There are 8 homozygotes in gnomad4. There are 284 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAPSS2 | NM_001015880.2 | c.276T>C | p.Ser92= | synonymous_variant | 3/13 | ENST00000456849.2 | |
PAPSS2 | NM_004670.4 | c.276T>C | p.Ser92= | synonymous_variant | 3/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAPSS2 | ENST00000456849.2 | c.276T>C | p.Ser92= | synonymous_variant | 3/13 | 1 | NM_001015880.2 | A1 | |
PAPSS2 | ENST00000361175.8 | c.276T>C | p.Ser92= | synonymous_variant | 3/12 | 1 | P4 | ||
PAPSS2 | ENST00000482258.1 | n.319T>C | non_coding_transcript_exon_variant | 3/3 | 5 | ||||
PAPSS2 | ENST00000465996.5 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00323 AC: 481AN: 149020Hom.: 5 Cov.: 28
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GnomAD3 exomes AF: 0.00617 AC: 1550AN: 251302Hom.: 21 AF XY: 0.00692 AC XY: 940AN XY: 135794
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GnomAD4 exome AF: 0.00326 AC: 4761AN: 1460304Hom.: 103 Cov.: 32 AF XY: 0.00386 AC XY: 2801AN XY: 726496
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GnomAD4 genome ? AF: 0.00331 AC: 494AN: 149136Hom.: 8 Cov.: 28 AF XY: 0.00391 AC XY: 284AN XY: 72658
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spondyloepimetaphyseal dysplasia, PAPSS2 type Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at