rs397515361
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_080424.4(SP110):c.642delC(p.Ser215AlafsTer14) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SP110
NM_080424.4 frameshift
NM_080424.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.660
Publications
6 publications found
Genes affected
SP110 (HGNC:5401): (SP110 nuclear body protein) The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This gene is a member of the SP100/SP140 family of nuclear body proteins and encodes a leukocyte-specific nuclear body component. The protein can function as an activator of gene transcription and may serve as a nuclear hormone receptor coactivator. In addition, it has been suggested that the protein may play a role in ribosome biogenesis and in the induction of myeloid cell differentiation. Alternative splicing has been observed for this gene and three transcript variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Jul 2008]
SP140 (HGNC:17133): (SP140 nuclear body protein) This gene encodes a member of the SP100 family of proteins, which are share common domains including an N-terminal homogeneously staining region domain followed by a SP100/autoimmune regulator/NucP41/P75/deformed epidermal autoregulatory factor domain, a plant homeobox zinc finger, and a bromodomain. The encoded protein is interferon-inducible and is expressed at high levels in the nuclei of leukocytes. Variants of this gene have been associated with multiple sclerosis, Crohn's disease, and chronic lymphocytic leukemia. Alternative splicing results in multiple variants. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-230212371-TG-T is Pathogenic according to our data. Variant chr2-230212371-TG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 5537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_080424.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SP110 | MANE Select | c.642delC | p.Ser215AlafsTer14 | frameshift | Exon 5 of 19 | NP_536349.3 | Q9HB58-6 | ||
| SP110 | c.660delC | p.Ser221AlafsTer14 | frameshift | Exon 6 of 20 | NP_001365371.1 | ||||
| SP110 | c.642delC | p.Ser215AlafsTer14 | frameshift | Exon 5 of 19 | NP_001365372.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SP110 | TSL:2 MANE Select | c.642delC | p.Ser215AlafsTer14 | frameshift | Exon 5 of 19 | ENSP00000258381.6 | Q9HB58-6 | ||
| SP110 | TSL:1 | c.642delC | p.Ser215AlafsTer14 | frameshift | Exon 5 of 18 | ENSP00000351488.4 | Q9HB58-1 | ||
| SP110 | TSL:1 | c.642delC | p.Ser215AlafsTer14 | frameshift | Exon 5 of 15 | ENSP00000258382.5 | Q9HB58-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461032Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726880 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461032
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
726880
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26128
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86230
European-Finnish (FIN)
AF:
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
AC:
1
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111222
Other (OTH)
AF:
AC:
0
AN:
60378
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
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1
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2
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0.60
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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10
<30
30-35
35-40
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
3
-
-
Hepatic veno-occlusive disease-immunodeficiency syndrome (4)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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