15-101274640-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_018445.6(SELENOS):c.360C>T(p.Asp120=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000953 in 1,613,504 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0051 ( 11 hom., cov: 33)
Exomes 𝑓: 0.00052 ( 5 hom. )
Consequence
SELENOS
NM_018445.6 synonymous
NM_018445.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.134
Genes affected
SELENOS (HGNC:30396): (selenoprotein S) This gene encodes a transmembrane protein that is localized in the endoplasmic reticulum (ER). It is involved in the degradation process of misfolded proteins in the ER, and may also have a role in inflammation control. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Two additional phylogenetically conserved stem-loop structures (Stem-loop 1 and Stem-loop 2) in the 3' UTR of this mRNA have been shown to function as modulators of Sec insertion. An alternatively spliced transcript variant, lacking the SECIS element and encoding a non-Sec containing shorter isoform, has been described for this gene (PMID:23614019). [provided by RefSeq, Jul 2017]
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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=-0.55).
BP6
?
Variant 15-101274640-G-A is Benign according to our data. Variant chr15-101274640-G-A is described in ClinVar as [Benign]. Clinvar id is 783723.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.134 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00507 (773/152342) while in subpopulation AFR AF= 0.0178 (739/41564). AF 95% confidence interval is 0.0167. There are 11 homozygotes in gnomad4. There are 371 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SELENOS | NM_018445.6 | c.360C>T | p.Asp120= | synonymous_variant | 4/6 | ENST00000526049.6 | |
SELENOS | NM_203472.3 | c.360C>T | p.Asp120= | synonymous_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SELENOS | ENST00000526049.6 | c.360C>T | p.Asp120= | synonymous_variant | 4/6 | 1 | NM_018445.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00499 AC: 760AN: 152224Hom.: 8 Cov.: 33
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GnomAD3 exomes AF: 0.00114 AC: 283AN: 248406Hom.: 4 AF XY: 0.000935 AC XY: 126AN XY: 134808
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GnomAD4 exome AF: 0.000524 AC: 765AN: 1461162Hom.: 5 Cov.: 31 AF XY: 0.000443 AC XY: 322AN XY: 726836
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 14, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at