Variant chr2-165953686-T-TCACCCGCTCACCCGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Strong

The NM_024753.5(TTC21B):c.19_20insGCGGGTGAGCGGGTG(p.Lys7delinsSerGlyTerAlaGlyGlu) variant causes a stop gained, conservative inframe insertion, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000177 in 56,570 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: 𝑓 0.000018 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TTC21B
NM_024753.5 stop_gained, conservative_inframe_insertion, splice_region

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.359

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 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 19 pathogenic variants in the truncated region.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC21B	NM_024753.5 link	c.19_20insGCGGGTGAGCGGGTG	p.Lys7delinsSerGlyTerAlaGlyGlu	stop_gained, conservative_inframe_insertion, splice_region_variant	Exon 1 of 29	ENST00000243344.8	NP_079029.3
TTC21B	XM_017004967.2 link	c.19_20insGCGGGTGAGCGGGTG	p.Lys7delinsSerGlyTerAlaGlyGlu	stop_gained, conservative_inframe_insertion, splice_region_variant	Exon 1 of 28		XP_016860456.1	A0A7P0TB61
TTC21B	XM_006712761.2 link	c.19_20insGCGGGTGAGCGGGTG	p.Lys7delinsSerGlyTerAlaGlyGlu	stop_gained, conservative_inframe_insertion, splice_region_variant	Exon 1 of 23		XP_006712824.1	A0A7P0TA66
TTC21B	XM_011511872.3 link	c.19_20insGCGGGTGAGCGGGTG	p.Lys7delinsSerGlyTerAlaGlyGlu	stop_gained, conservative_inframe_insertion, splice_region_variant	Exon 1 of 21		XP_011510174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC21B	ENST00000243344.8 link	c.19_20insGCGGGTGAGCGGGTG	p.Lys7delinsSerGlyTerAlaGlyGlu	stop_gained, conservative_inframe_insertion, splice_region_variant	Exon 1 of 29	1	NM_024753.5	ENSP00000243344.7		Q7Z4L5-1

Frequencies

GnomAD3 genomes

AF:

0.0000177

AC:

AN:

56570

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000713

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000718

AC:

AN:

556982

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

279116

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000177

AC:

AN:

56570

Hom.:

Cov.:

AF XY:

0.0000361

AC XY:

AN XY:

27698

show subpopulations

Gnomad4 AFR

AF:

0.0000713

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over