rs777801181
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024753.5(TTC21B):āc.1643C>Gā(p.Ser548Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000089 ( 0 hom. )
Consequence
TTC21B
NM_024753.5 missense
NM_024753.5 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 9.96
Genes affected
TTC21B (HGNC:25660): (tetratricopeptide repeat domain 21B) This gene encodes a member of TTC21 family, containing several tetratricopeptide repeat (TPR) domains. This protein is localized to the cilium axoneme, and may play a role in retrograde intraflagellar transport in cilia. Mutations in this gene are associated with various ciliopathies, nephronophthisis 12, and asphyxiating thoracic dystrophy 4. [provided by RefSeq, Oct 2011]
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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;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC21B | NM_024753.5 | c.1643C>G | p.Ser548Cys | missense_variant | 13/29 | ENST00000243344.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC21B | ENST00000243344.8 | c.1643C>G | p.Ser548Cys | missense_variant | 13/29 | 1 | NM_024753.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251284Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135798
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461786Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727198
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GnomAD4 genome ? Cov.: 32
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32
ExAC
?
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6
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Jeune thoracic dystrophy;C0687120:Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 03, 2022 | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 548 of the TTC21B protein (p.Ser548Cys). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 459286). This variant has not been reported in the literature in individuals affected with TTC21B-related conditions. This variant is present in population databases (rs777801181, gnomAD 0.01%). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Gain of catalytic residue at L549 (P = 0.0112);
MVP
MPC
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