2-112494341-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_153712.5(TTL):c.435C>T(p.Asn145Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00068 in 1,614,116 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00063 ( 9 hom. )
Consequence
TTL
NM_153712.5 synonymous
NM_153712.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.29
Genes affected
TTL (HGNC:21586): (tubulin tyrosine ligase) TTL is a cytosolic enzyme involved in the posttranslational modification of alpha-tubulin (see MIM 602529). Alpha-tubulin within assembled microtubules is detyrosinated over time at the C terminus. After microtubule disassembly, TTL restores the tyrosine residues and consequently participates in a cycle of tubulin detyrosination and tyrosination (Erck et al., 2003 [PubMed 14571137]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 2-112494341-C-T is Benign according to our data. Variant chr2-112494341-C-T is described in ClinVar as [Benign]. Clinvar id is 788847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.29 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000631 (922/1461800) while in subpopulation AMR AF= 0.0193 (865/44714). AF 95% confidence interval is 0.0183. There are 9 homozygotes in gnomad4_exome. There are 390 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTL | NM_153712.5 | c.435C>T | p.Asn145Asn | synonymous_variant | Exon 3 of 7 | ENST00000233336.7 | NP_714923.1 | |
TTL | NM_001371712.1 | c.435C>T | p.Asn145Asn | synonymous_variant | Exon 3 of 7 | NP_001358641.1 | ||
TTL | XM_005263599.4 | c.435C>T | p.Asn145Asn | synonymous_variant | Exon 3 of 7 | XP_005263656.1 | ||
TTL | XM_011510665.3 | c.435C>T | p.Asn145Asn | synonymous_variant | Exon 3 of 6 | XP_011508967.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00113 AC: 172AN: 152198Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00282 AC: 705AN: 249712Hom.: 7 AF XY: 0.00218 AC XY: 295AN XY: 135134
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GnomAD4 exome AF: 0.000631 AC: 922AN: 1461800Hom.: 9 Cov.: 32 AF XY: 0.000536 AC XY: 390AN XY: 727198
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GnomAD4 genome AF: 0.00115 AC: 175AN: 152316Hom.: 3 Cov.: 32 AF XY: 0.00136 AC XY: 101AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Apr 13, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at