rs192919234
Variant summary
Our verdict is Pathogenic. Variant got 20 ACMG points: 20P and 0B. PVS1PM2PP3_ModeratePP5_Very_Strong
The NM_020461.4(TUBGCP6):c.895C>T(p.Arg299Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,754 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
Consequence
NM_020461.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBGCP6 | NM_020461.4 | c.895C>T | p.Arg299Ter | stop_gained | 2/25 | ENST00000248846.10 | |
TUBGCP6 | XR_001755343.3 | n.1459C>T | non_coding_transcript_exon_variant | 2/20 | |||
TUBGCP6 | XR_007067982.1 | n.1459C>T | non_coding_transcript_exon_variant | 2/19 | |||
TUBGCP6 | XR_938347.3 | n.1459C>T | non_coding_transcript_exon_variant | 2/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBGCP6 | ENST00000248846.10 | c.895C>T | p.Arg299Ter | stop_gained | 2/25 | 1 | NM_020461.4 | P1 | |
TUBGCP6 | ENST00000439308.6 | c.895C>T | p.Arg299Ter | stop_gained | 2/25 | 1 | |||
TUBGCP6 | ENST00000498611.5 | n.1428C>T | non_coding_transcript_exon_variant | 2/23 | 1 | ||||
TUBGCP6 | ENST00000434349.1 | c.136+11C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152160Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250758Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135732
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461476Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727008
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152278Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6AN XY: 74466
ClinVar
Submissions by phenotype
Microcephaly and chorioretinopathy 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | DASA | Nov 03, 2022 | The c.895C>T;p.(Arg299*) variant creates a premature translational stop signal in the TUBGCP6 gene. It is expected to result in an absent or disrupted protein product - PVS1. ClinVar contains an entry for this variant (Clinvar ID:212517) - PS4_supporting. The variant is present at low allele frequencies population databases (rs192919234 – gnomAD 0.0002127%; ABraOM 0.000427 frequency - https://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 08, 2022 | This sequence change creates a premature translational stop signal (p.Arg299*) in the TUBGCP6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TUBGCP6 are known to be pathogenic (PMID: 25344692). This variant is present in population databases (rs192919234, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TUBGCP6-related conditions. ClinVar contains an entry for this variant (Variation ID: 212517). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Microcephaly and chorioretinopathy with or without intellectual disability Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 12, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at