1-243270236-G-T
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006642.5(SDCCAG8):c.199G>T(p.Glu67*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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
SDCCAG8
NM_006642.5 stop_gained
NM_006642.5 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 5.47
Genes affected
SDCCAG8 (HGNC:10671): (SHH signaling and ciliogenesis regulator SDCCAG8) This gene encodes a centrosome associated protein. This protein may be involved in organizing the centrosome during interphase and mitosis. Mutations in this gene are associated with retinal-renal ciliopathy. [provided by RefSeq, Oct 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 1-243270236-G-T is Pathogenic according to our data. Variant chr1-243270236-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 591885.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SDCCAG8 | NM_006642.5 | c.199G>T | p.Glu67* | stop_gained | 2/18 | ENST00000366541.8 | NP_006633.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SDCCAG8 | ENST00000366541.8 | c.199G>T | p.Glu67* | stop_gained | 2/18 | 1 | NM_006642.5 | ENSP00000355499.3 | ||
SDCCAG8 | ENST00000490065.5 | n.352G>T | non_coding_transcript_exon_variant | 2/5 | 4 | |||||
SDCCAG8 | ENST00000491888.1 | n.210G>T | non_coding_transcript_exon_variant | 2/3 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461784Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727172
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Senior-Loken syndrome 7;C3889474:Bardet-Biedl syndrome 16 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 04, 2020 | This sequence change creates a premature translational stop signal (p.Glu67*) in the SDCCAG8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDCCAG8 are known to be pathogenic (PMID: 20835237, 22190896). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with SDCCAG8-related conditions. ClinVar contains an entry for this variant (Variation ID: 591885). This variant is not present in population databases (ExAC no frequency). - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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