chr22-27983132-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_001145418.2(TTC28):c.6535C>T(p.Arg2179Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00227 in 1,551,802 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0023 ( 4 hom. )
Consequence
TTC28
NM_001145418.2 missense
NM_001145418.2 missense
Scores
1
8
6
Clinical Significance
Conservation
PhyloP100: 5.84
Genes affected
TTC28 (HGNC:29179): (tetratricopeptide repeat domain 28) Enables kinase binding activity. Involved in regulation of mitotic cell cycle. Located in midbody. [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.
PP2
?
Missense variant where missense usually causes diseases, TTC28
BP4
?
Computational evidence support a benign effect (MetaRNN=0.011893421).
BP6
?
Variant 22-27983132-G-A is Benign according to our data. Variant chr22-27983132-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 774361.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS2
?
High Homozygotes in GnomAdExome at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC28 | NM_001145418.2 | c.6535C>T | p.Arg2179Cys | missense_variant | 23/23 | ENST00000397906.7 | |
TTC28-AS1 | NR_026963.1 | n.251-11341G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC28 | ENST00000397906.7 | c.6535C>T | p.Arg2179Cys | missense_variant | 23/23 | 1 | NM_001145418.2 | P1 | |
TTC28-AS1 | ENST00000454741.5 | n.206-11341G>A | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00174 AC: 265AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00145 AC: 228AN: 156834Hom.: 2 AF XY: 0.00164 AC XY: 136AN XY: 83088
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GnomAD4 exome AF: 0.00233 AC: 3260AN: 1399496Hom.: 4 Cov.: 32 AF XY: 0.00235 AC XY: 1624AN XY: 690252
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 30, 2021 | The c.6535C>T (p.R2179C) alteration is located in exon 23 (coding exon 23) of the TTC28 gene. This alteration results from a C to T substitution at nucleotide position 6535, causing the arginine (R) at amino acid position 2179 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
0.34
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at