Variant 14-88840976-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144596.4(TTC8):c.329+48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,613,606 control chromosomes in the GnomAD database, including 45,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3374 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42229 hom. )

Consequence

TTC8
NM_144596.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.552

Variant links:

Genes affected

TTC8 (HGNC:20087): (tetratricopeptide repeat domain 8) This gene encodes a protein that has been directly linked to Bardet-Biedl syndrome. The primary features of this syndrome include retinal dystrophy, obesity, polydactyly, renal abnormalities and learning disabilities. Experimentation in non-human eukaryotes suggests that this gene is expressed in ciliated cells and that it is involved in the formation of cilia. A mutation in this gene has also been implicated in nonsyndromic retinitis pigmentosa. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

TTC8 links:

TTC8 (HGNC:):

TTC8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 14-88840976-T-C is Benign according to our data. Variant chr14-88840976-T-C is described in ClinVar as [Benign]. Clinvar id is 262516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC8	NM_144596.4 linkuse as main transcript	c.329+48T>C		intron_variant		ENST00000380656.7	NP_653197.2	Q8TAM2-4Q86U25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC8	ENST00000380656.7 linkuse as main transcript	c.329+48T>C		intron_variant		2	NM_144596.4	ENSP00000370031.2		Q8TAM2-4

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30046

AN:

152040

Hom.:

3366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0972

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.179

GnomAD3 exomes

AF:

0.212

AC:

53296

AN:

251174

Hom.:

6065

AF XY:

0.211

AC XY:

28635

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.0974

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.217

Gnomad EAS exome

AF:

0.307

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.214

Gnomad NFE exome

AF:

0.241

Gnomad OTH exome

AF:

0.208

GnomAD4 exome

AF:

0.236

AC:

345386

AN:

1461448

Hom.:

42229

Cov.:

AF XY:

0.234

AC XY:

170360

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.0876

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.217

Gnomad4 EAS exome

AF:

0.316

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.217

Gnomad4 NFE exome

AF:

0.249

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.198

AC:

30077

AN:

152158

Hom.:

3374

Cov.:

AF XY:

0.195

AC XY:

14474

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0971

Gnomad4 AMR

AF:

0.197

Gnomad4 ASJ

AF:

0.219

Gnomad4 EAS

AF:

0.318

Gnomad4 SAS

AF:

0.178

Gnomad4 FIN

AF:

0.214

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.177

Alfa

AF:

0.217

Hom.:

1091

Bravo

AF:

0.193

Asia WGS

AF:

0.221

AC:

768

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.52

DANN

Benign

0.70

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