rs759086770
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_024753.5(TTC21B):āc.3605T>Cā(p.Leu1202Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,828 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 Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000082 ( 0 hom. )
Consequence
TTC21B
NM_024753.5 missense
NM_024753.5 missense
Scores
12
4
3
Clinical Significance
Conservation
PhyloP100: 9.32
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 Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.945
PP5
?
Variant 2-165883873-A-G is Pathogenic according to our data. Variant chr2-165883873-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 446651.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC21B | NM_024753.5 | c.3605T>C | p.Leu1202Pro | missense_variant | 26/29 | ENST00000243344.8 | |
TTC21B | XM_017004967.2 | c.3605T>C | p.Leu1202Pro | missense_variant | 26/28 | ||
TTC21B | XM_047445870.1 | c.2951T>C | p.Leu984Pro | missense_variant | 22/25 | ||
TTC21B | XM_011511871.4 | c.2855T>C | p.Leu952Pro | missense_variant | 21/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC21B | ENST00000243344.8 | c.3605T>C | p.Leu1202Pro | missense_variant | 26/29 | 1 | NM_024753.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461828Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727218
GnomAD4 exome
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12
AN:
1461828
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32
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AC XY:
5
AN XY:
727218
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Type IV short rib polydactyly syndrome Pathogenic:2
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Pathogenic, no assertion criteria provided | research | Dan Cohn Lab, University Of California Los Angeles | Jun 01, 2017 | - - |
Asphyxiating thoracic dystrophy 4 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 18, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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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