chr11-113324643-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_017868.4(TTC12):c.283C>T(p.Arg95Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,613,774 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
TTC12
NM_017868.4 stop_gained
NM_017868.4 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 2.17
Genes affected
TTC12 (HGNC:23700): (tetratricopeptide repeat domain 12) Involved in axonemal dynein complex assembly and sperm axoneme assembly. Located in centrosome and cytoplasm. Implicated in primary ciliary dyskinesia 45. [provided by Alliance of Genome Resources, Apr 2022]
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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 11-113324643-C-T is Pathogenic according to our data. Variant chr11-113324643-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2377549.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC12 | NM_017868.4 | c.283C>T | p.Arg95Ter | stop_gained | 5/22 | ENST00000529221.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC12 | ENST00000529221.6 | c.283C>T | p.Arg95Ter | stop_gained | 5/22 | 2 | NM_017868.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152098Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251150Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135738
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GnomAD4 exome AF: 0.000117 AC: 171AN: 1461676Hom.: 0 Cov.: 31 AF XY: 0.000114 AC XY: 83AN XY: 727136
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74302
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 10, 2022 | The c.283C>T (p.R95*) alteration, located in exon 5 (coding exon 4) of the TTC12 gene, consists of a C to T substitution at nucleotide position 283. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 95. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of 0.004% (11/251150) total alleles studied. The highest observed frequency was 0.01% (1/10072) of Ashkenazi Jewish alleles. Based on the available evidence, this alteration is classified as pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -38
Find out detailed SpliceAI scores and Pangolin per-transcript scores at