14-20296391-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_138376.3(TTC5):c.695C>T(p.Thr232Met) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000422 in 1,611,756 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000032 ( 2 hom. )
Consequence
TTC5
NM_138376.3 missense, splice_region
NM_138376.3 missense, splice_region
Scores
1
8
10
Splicing: ADA: 0.9915
2
Clinical Significance
Conservation
PhyloP100: 5.32
Genes affected
TTC5 (HGNC:19274): (tetratricopeptide repeat domain 5) Predicted to enable DNA binding activity and chromatin binding activity. Predicted to be involved in DNA repair. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTC5 | ENST00000258821.8 | c.695C>T | p.Thr232Met | missense_variant, splice_region_variant | 6/10 | 1 | NM_138376.3 | ENSP00000258821.3 | ||
TTC5 | ENST00000383029.7 | n.*240C>T | splice_region_variant, non_coding_transcript_exon_variant | 6/10 | 1 | ENSP00000372496.3 | ||||
TTC5 | ENST00000383029.7 | n.*240C>T | 3_prime_UTR_variant | 6/10 | 1 | ENSP00000372496.3 | ||||
TTC5 | ENST00000554157.5 | n.706C>T | splice_region_variant, non_coding_transcript_exon_variant | 6/9 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152112Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251426Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135878
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GnomAD4 exome AF: 0.0000322 AC: 47AN: 1459526Hom.: 2 Cov.: 28 AF XY: 0.0000372 AC XY: 27AN XY: 726290
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74434
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 25, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously reported as a pathogenic or benign germline variant to our knowledge; This variant is associated with the following publications: (PMID: 22996961) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at