rs80225158

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_024753.5(TTC21B):c.2385G>C(p.Leu795Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,613,778 control chromosomes in the GnomAD database, including 703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 126 hom., cov: 32)

Exomes 𝑓: 0.013 ( 577 hom. )

Consequence

TTC21B
NM_024753.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 2.62

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 2-165911403-C-G is Benign according to our data. Variant chr2-165911403-C-G is described in ClinVar as [Benign]. Clinvar id is 96138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-165911403-C-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC21B	NM_024753.5 link	c.2385G>C	p.Leu795Leu	synonymous_variant	Exon 18 of 29	ENST00000243344.8	NP_079029.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC21B	ENST00000243344.8 link	c.2385G>C	p.Leu795Leu	synonymous_variant	Exon 18 of 29	1	NM_024753.5	ENSP00000243344.7		Q7Z4L5-1

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2975

AN:

152064

Hom.:

125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.0636

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.0241

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00670

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0297

AC:

7455

AN:

251202

Hom.:

400

AF XY:

0.0245

AC XY:

3320

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00818

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.00457

Gnomad EAS exome

AF:

0.0669

Gnomad SAS exome

AF:

0.00356

Gnomad FIN exome

AF:

0.0231

Gnomad NFE exome

AF:

0.00642

Gnomad OTH exome

AF:

0.0219

GnomAD4 exome

AF:

0.0129

AC:

18887

AN:

1461598

Hom.:

577

Cov.:

AF XY:

0.0121

AC XY:

8762

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00660

Gnomad4 AMR exome

AF:

0.129

Gnomad4 ASJ exome

AF:

0.00410

Gnomad4 EAS exome

AF:

0.0748

Gnomad4 SAS exome

AF:

0.00332

Gnomad4 FIN exome

AF:

0.0223

Gnomad4 NFE exome

AF:

0.00684

Gnomad4 OTH exome

AF:

0.0119

GnomAD4 genome

AF:

0.0195

AC:

2973

AN:

152180

Hom.:

126

Cov.:

AF XY:

0.0215

AC XY:

1603

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00696

Gnomad4 AMR

AF:

0.103

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.0634

Gnomad4 SAS

AF:

0.00498

Gnomad4 FIN

AF:

0.0241

Gnomad4 NFE

AF:

0.00671

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00605

Hom.:

Bravo

AF:

0.0258

Asia WGS

AF:

0.0280

AC:

AN:

3476

EpiCase

AF:

0.00676

EpiControl

AF:

0.00587

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 08, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Oct 10, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Oct 21, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Asphyxiating thoracic dystrophy 4

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jeune thoracic dystrophy;C0687120:Nephronophthisis

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nephronophthisis 12

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Connective tissue disorder

Benign:1

May 26, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

5.7

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over