chr21-37095344-T-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_001330683.2(TTC3):c.688-6T>C variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.000357 in 1,592,128 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 1 hom. )
Consequence
TTC3
NM_001330683.2 splice_region, splice_polypyrimidine_tract, intron
NM_001330683.2 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.01335
2
Clinical Significance
Conservation
PhyloP100: 4.62
Genes affected
TTC3 (HGNC:12393): (tetratricopeptide repeat domain 3) Enables ubiquitin-protein transferase activity. Involved in protein K48-linked ubiquitination and ubiquitin-dependent protein catabolic process. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
?
Variant 21-37095344-T-C is Benign according to our data. Variant chr21-37095344-T-C is described in ClinVar as [Benign]. Clinvar id is 769126.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC3 | NM_001330683.2 | c.688-6T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000418766.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC3 | ENST00000418766.6 | c.688-6T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001330683.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00145 AC: 221AN: 152138Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000496 AC: 117AN: 235656Hom.: 1 AF XY: 0.000447 AC XY: 57AN XY: 127490
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GnomAD4 exome AF: 0.000240 AC: 346AN: 1439872Hom.: 1 Cov.: 29 AF XY: 0.000234 AC XY: 168AN XY: 716480
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at