rs587777471
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_015072.5(TTLL5):c.3354G>A(p.Trp1118Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000137 in 1,459,796 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 (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 29)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
TTLL5
NM_015072.5 stop_gained
NM_015072.5 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 5.73
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 11 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 14-75863694-G-A is Pathogenic according to our data. Variant chr14-75863694-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 139515.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-75863694-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTLL5 | NM_015072.5 | c.3354G>A | p.Trp1118Ter | stop_gained | 29/32 | ENST00000298832.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTLL5 | ENST00000298832.14 | c.3354G>A | p.Trp1118Ter | stop_gained | 29/32 | 1 | NM_015072.5 | P4 | |
TTLL5 | ENST00000557636.5 | c.3399G>A | p.Trp1133Ter | stop_gained | 30/32 | 1 | A2 | ||
TTLL5 | ENST00000556893.5 | c.2007G>A | p.Trp669Ter | stop_gained | 15/17 | 1 | |||
TTLL5 | ENST00000554510.5 | c.1881G>A | p.Trp627Ter | stop_gained | 14/16 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 29
GnomAD3 genomes
?
Cov.:
29
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459796Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726140
GnomAD4 exome
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2
AN:
1459796
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31
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2
AN XY:
726140
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GnomAD4 genome ? Cov.: 29
GnomAD4 genome
?
Cov.:
29
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Cone-rod dystrophy 19 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A;A
Vest4
GERP RS
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