chr22-27982964-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001145418.2(TTC28):c.6703C>A(p.Pro2235Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,551,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
TTC28
NM_001145418.2 missense
NM_001145418.2 missense
Scores
4
5
6
Clinical Significance
Conservation
PhyloP100: 9.31
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, TTC28
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3329411).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC28 | NM_001145418.2 | c.6703C>A | p.Pro2235Thr | missense_variant | 23/23 | ENST00000397906.7 | |
TTC28-AS1 | NR_026963.1 | n.251-11509G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC28 | ENST00000397906.7 | c.6703C>A | p.Pro2235Thr | missense_variant | 23/23 | 1 | NM_001145418.2 | P1 | |
TTC28-AS1 | ENST00000454741.5 | n.206-11509G>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152166Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000512 AC: 8AN: 156324Hom.: 0 AF XY: 0.0000603 AC XY: 5AN XY: 82870
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GnomAD4 exome AF: 0.0000157 AC: 22AN: 1399414Hom.: 0 Cov.: 32 AF XY: 0.0000188 AC XY: 13AN XY: 690214
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 04, 2022 | The c.6703C>A (p.P2235T) alteration is located in exon 23 (coding exon 23) of the TTC28 gene. This alteration results from a C to A substitution at nucleotide position 6703, causing the proline (P) at amino acid position 2235 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Pathogenic
D
MutationTaster
Benign
D
PrimateAI
Benign
T
Sift4G
Benign
T;T
Polyphen
1.0
.;D
Vest4
0.30
MutPred
0.23
.;Gain of phosphorylation at P2235 (P = 0.0041);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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