NM_024753.5:c.19_20insGGGTG

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_024753.5(TTC21B):​c.19_20insGGGTG​(p.Lys7ArgfsTer5) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000898 in 557,028 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 26)
Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

TTC21B
NM_024753.5 frameshift, splice_region

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.359

Publications

0 publications found
Variant links:
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]
TTC21B Gene-Disease associations (from GenCC):
  • nephronophthisis 12
    Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
  • asphyxiating thoracic dystrophy 4
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • Jeune syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • nephronophthisis 2
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 105 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TTC21BNM_024753.5 linkc.19_20insGGGTG p.Lys7ArgfsTer5 frameshift_variant, splice_region_variant Exon 1 of 29 ENST00000243344.8 NP_079029.3
TTC21BXM_017004967.2 linkc.19_20insGGGTG p.Lys7ArgfsTer5 frameshift_variant, splice_region_variant Exon 1 of 28 XP_016860456.1 A0A7P0TB61
TTC21BXM_006712761.2 linkc.19_20insGGGTG p.Lys7ArgfsTer5 frameshift_variant, splice_region_variant Exon 1 of 23 XP_006712824.1 A0A7P0TA66
TTC21BXM_011511872.3 linkc.19_20insGGGTG p.Lys7ArgfsTer5 frameshift_variant, splice_region_variant Exon 1 of 21 XP_011510174.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TTC21BENST00000243344.8 linkc.19_20insGGGTG p.Lys7ArgfsTer5 frameshift_variant, splice_region_variant Exon 1 of 29 1 NM_024753.5 ENSP00000243344.7 Q7Z4L5-1

Frequencies

GnomAD3 genomes
Cov.:
26
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
54534
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000898
AC:
5
AN:
557028
Hom.:
0
Cov.:
36
AF XY:
0.0000107
AC XY:
3
AN XY:
279136
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
12208
American (AMR)
AF:
0.00
AC:
0
AN:
11324
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
10652
East Asian (EAS)
AF:
0.00
AC:
0
AN:
21502
South Asian (SAS)
AF:
0.00
AC:
0
AN:
39616
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
25112
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2740
European-Non Finnish (NFE)
AF:
0.0000122
AC:
5
AN:
408310
Other (OTH)
AF:
0.00
AC:
0
AN:
25564
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs759648976; hg19: chr2-166810196; API