1-83870039-T-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_024686.6(TTLL7):c.2587A>G(p.Thr863Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000196 in 1,584,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
TTLL7
NM_024686.6 missense
NM_024686.6 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: -0.115
Publications
0 publications found
Genes affected
TTLL7 (HGNC:26242): (tubulin tyrosine ligase like 7) Enables alpha-tubulin binding activity; beta-tubulin binding activity; and tubulin-glutamic acid ligase activity. Involved in protein polyglutamylation. Predicted to be located in 9+0 non-motile cilium and ciliary basal body. Predicted to be active in cilium. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0256145).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TTLL7 | NM_024686.6 | c.2587A>G | p.Thr863Ala | missense_variant | Exon 21 of 21 | ENST00000260505.13 | NP_078962.4 | |
| TTLL7 | NM_001350214.2 | c.2587A>G | p.Thr863Ala | missense_variant | Exon 22 of 22 | NP_001337143.1 | ||
| TTLL7 | NM_001350215.2 | c.2506A>G | p.Thr836Ala | missense_variant | Exon 20 of 20 | NP_001337144.1 | ||
| TTLL7 | XM_047430691.1 | c.1852A>G | p.Thr618Ala | missense_variant | Exon 15 of 15 | XP_047286647.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152172
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000267 AC: 6AN: 224836 AF XY: 0.0000245 show subpopulations
GnomAD2 exomes
AF:
AC:
6
AN:
224836
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000202 AC: 29AN: 1432490Hom.: 0 Cov.: 30 AF XY: 0.0000197 AC XY: 14AN XY: 712096 show subpopulations
GnomAD4 exome
AF:
AC:
29
AN:
1432490
Hom.:
Cov.:
30
AF XY:
AC XY:
14
AN XY:
712096
show subpopulations
African (AFR)
AF:
AC:
1
AN:
31708
American (AMR)
AF:
AC:
2
AN:
37272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25416
East Asian (EAS)
AF:
AC:
2
AN:
37790
South Asian (SAS)
AF:
AC:
3
AN:
80550
European-Finnish (FIN)
AF:
AC:
0
AN:
53206
Middle Eastern (MID)
AF:
AC:
1
AN:
5712
European-Non Finnish (NFE)
AF:
AC:
19
AN:
1101646
Other (OTH)
AF:
AC:
1
AN:
59190
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.468
Heterozygous variant carriers
0
2
3
5
6
8
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74322 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152172
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74322
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41444
American (AMR)
AF:
AC:
0
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5202
South Asian (SAS)
AF:
AC:
1
AN:
4826
European-Finnish (FIN)
AF:
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68022
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
0
ALSPAC
AF:
AC:
1
ExAC
AF:
AC:
4
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Sep 26, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.2587A>G (p.T863A) alteration is located in exon 21 (coding exon 20) of the TTLL7 gene. This alteration results from a A to G substitution at nucleotide position 2587, causing the threonine (T) at amino acid position 863 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
PhyloP100
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of sheet (P = 0.0315);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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