dbSNP rs183060026: TTC8:c.*16C>T (chr14-88877426-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_144596.4(TTC8):c.*16C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00065 in 1,590,332 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 2 hom. )

Consequence

TTC8
NM_144596.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0670

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 8
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
retinitis pigmentosa 51
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
TTC8-related ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TTC8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-88877426-C-T is Benign according to our data. Variant chr14-88877426-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 262511.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000519 (79/152228) while in subpopulation NFE AF = 0.000544 (37/68010). AF 95% confidence interval is 0.000405. There are 0 homozygotes in GnomAd4. There are 48 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144596.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTC8	NM_144596.4	MANE Select	c.*16C>T	3_prime_UTR	Exon 15 of 15	NP_653197.2
TTC8	NM_001288781.1		c.*16C>T	3_prime_UTR	Exon 16 of 16	NP_001275710.1	Q86U25
TTC8	NM_198309.3		c.*16C>T	3_prime_UTR	Exon 15 of 15	NP_938051.1	A0A0C4DGY3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTC8	ENST00000380656.7	TSL:2 MANE Select	c.*16C>T	3_prime_UTR	Exon 15 of 15	ENSP00000370031.2	Q8TAM2-4
TTC8	ENST00000338104.10	TSL:1	c.*16C>T	3_prime_UTR	Exon 15 of 15	ENSP00000337653.6	A0A0C4DGX9
TTC8	ENST00000622513.4	TSL:1	c.*16C>T	3_prime_UTR	Exon 14 of 14	ENSP00000482721.1	A0A0C4DGY3

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00293

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000586

AC:

147

AN:

251020

AF XY:

0.000686

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00208

Gnomad NFE exome

AF:

0.000802

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.000664

AC:

955

AN:

1438104

Hom.:

Cov.:

AF XY:

0.000625

AC XY:

448

AN XY:

717156

show subpopulations

African (AFR)

AF:

0.000212

AC:

AN:

32958

American (AMR)

AF:

0.0000224

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25980

East Asian (EAS)

AF:

0.00

AC:

AN:

39542

South Asian (SAS)

AF:

0.00

AC:

AN:

85770

European-Finnish (FIN)

AF:

0.00215

AC:

115

AN:

53366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.000738

AC:

805

AN:

1090532

Other (OTH)

AF:

0.000453

AC:

AN:

59562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

133

178

222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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

AF:

0.000519

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41548

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00293

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68010

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000717

Hom.:

Bravo

AF:

0.000264

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.3

(source)

DANN

Benign

0.53

PhyloP100

-0.067

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over