1-54787064-A-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001114108.2(TTC22):c.751T>C(p.Cys251Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 1,525,608 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000015 ( 0 hom. )
Consequence
TTC22
NM_001114108.2 missense
NM_001114108.2 missense
Scores
5
9
5
Clinical Significance
Conservation
PhyloP100: 8.12
Publications
0 publications found
Genes affected
TTC22 (HGNC:26067): (tetratricopeptide repeat domain 22) This gene encodes a protein with seven tetratricopeptide (TPR) repeats. Tetratricopeptide repeat containing motifs are found in a variety of proteins and may mediate protein-protein interactions and chaperone activity. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2011]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.863
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TTC22 | NM_001114108.2 | c.751T>C | p.Cys251Arg | missense_variant | Exon 4 of 7 | ENST00000371276.9 | NP_001107580.1 | |
| TTC22 | NM_017904.4 | c.751T>C | p.Cys251Arg | missense_variant | Exon 4 of 6 | NP_060374.2 | ||
| TTC22 | XM_011541671.3 | c.751T>C | p.Cys251Arg | missense_variant | Exon 4 of 6 | XP_011539973.1 | ||
| TTC22 | XM_017001582.2 | c.178T>C | p.Cys60Arg | missense_variant | Exon 4 of 7 | XP_016857071.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000659 AC: 1AN: 151814Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151814
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000146 AC: 2AN: 1373794Hom.: 0 Cov.: 29 AF XY: 0.00000296 AC XY: 2AN XY: 675722 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1373794
Hom.:
Cov.:
29
AF XY:
AC XY:
2
AN XY:
675722
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
31334
American (AMR)
AF:
AC:
0
AN:
32554
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23022
East Asian (EAS)
AF:
AC:
0
AN:
35918
South Asian (SAS)
AF:
AC:
0
AN:
74554
European-Finnish (FIN)
AF:
AC:
0
AN:
48672
Middle Eastern (MID)
AF:
AC:
0
AN:
5002
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1065794
Other (OTH)
AF:
AC:
0
AN:
56944
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000659 AC: 1AN: 151814Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74148 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151814
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74148
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41294
American (AMR)
AF:
AC:
0
AN:
15250
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5130
South Asian (SAS)
AF:
AC:
0
AN:
4804
European-Finnish (FIN)
AF:
AC:
0
AN:
10608
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67948
Other (OTH)
AF:
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Apr 20, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.751T>C (p.C251R) alteration is located in exon 4 (coding exon 4) of the TTC22 gene. This alteration results from a T to C substitution at nucleotide position 751, causing the cysteine (C) at amino acid position 251 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0036);Gain of MoRF binding (P = 0.0036);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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