11-8038922-G-T
Variant names:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_003320.5(TUB):c.49G>T(p.Glu17*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
TUB
NM_003320.5 stop_gained
NM_003320.5 stop_gained
Scores
1
6
Clinical Significance
Conservation
PhyloP100: -2.82
Genes affected
TUB (HGNC:12406): (TUB bipartite transcription factor) This gene encodes a member of the Tubby family of bipartite transcription factors. The encoded protein may play a role in obesity and sensorineural degradation. The crystal structure has been determined for a similar protein in mouse, and it functions as a membrane-bound transcription regulator that translocates to the nucleus in response to phosphoinositide hydrolysis. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.971 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TUB | NM_003320.5 | c.49G>T | p.Glu17* | stop_gained | Exon 1 of 13 | NP_003311.2 | ||
TUB | XM_005253109.4 | c.164+19564G>T | intron_variant | Intron 1 of 11 | XP_005253166.1 | |||
TUB | XM_047427512.1 | c.164+19564G>T | intron_variant | Intron 1 of 11 | XP_047283468.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TUB | ENST00000305253.8 | c.49G>T | p.Glu17* | stop_gained | Exon 1 of 13 | 1 | ENSP00000305426.4 | |||
TUB | ENST00000534099.5 | c.56+19564G>T | intron_variant | Intron 1 of 11 | 2 | ENSP00000434400.1 | ||||
ENSG00000254921 | ENST00000528151.1 | n.264C>A | non_coding_transcript_exon_variant | Exon 2 of 2 | 4 | |||||
ENSG00000254921 | ENST00000526646.2 | n.202+595C>A | intron_variant | Intron 1 of 1 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461666Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727126
GnomAD4 exome
AF:
AC:
1
AN:
1461666
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
727126
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 21, 2022 | This sequence change creates a premature translational stop signal (p.Glu17*) in the TUB gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TUB cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TUB-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
Vest4
GERP RS
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at