rs587777469
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015072.5(TTLL5):c.1586_1589del(p.Glu529ValfsTer2) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000137 in 1,461,814 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: 0.0000014 ( 0 hom. )
Consequence
TTLL5
NM_015072.5 frameshift
NM_015072.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.08
Genes affected
TTLL5 (HGNC:19963): (tubulin tyrosine ligase like 5) This gene encodes a member of the tubulin tyrosine ligase like protein family. This protein interacts with two glucocorticoid receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. This protein may function as a coregulator of glucocorticoid receptor mediated gene induction and repression. This protein may also function as an alpha tubulin polyglutamylase.[provided by RefSeq, Feb 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 14-75764647-TAGAG-T is Pathogenic according to our data. Variant chr14-75764647-TAGAG-T is described in ClinVar as [Pathogenic]. Clinvar id is 139513.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-75764647-TAGAG-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTLL5 | NM_015072.5 | c.1586_1589del | p.Glu529ValfsTer2 | frameshift_variant | 19/32 | ENST00000298832.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTLL5 | ENST00000298832.14 | c.1586_1589del | p.Glu529ValfsTer2 | frameshift_variant | 19/32 | 1 | NM_015072.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251160Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135716
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461814Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727204
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cone-rod dystrophy 19 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2014 | - - |
Cone-rod dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel | Jul 24, 2023 | Clinical significance based on ACMG v2.0 - |
Computational scores
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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