rs79747892

Variant names:

• chr14-88877282-T-C
• rs79747892
• NM_144596.4:c.1432-12T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144596.4(TTC8):​c.1432-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00623 in 1,606,928 control chromosomes in the GnomAD database, including 560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (298 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (262 hom.)
• Consequence: TTC8 NM_144596.4 intron
• Scores: Splicing: ADA: 0.0001204
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.638
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 14-88877282-T-C is Benign according to our data. Variant chr14-88877282-T-C is described in ClinVar as Benign. ClinVar VariationId is 262514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC8	NM_144596.4	MANE Select	c.1432-12T>C		intron	N/A	NP_653197.2
	TTC8	NM_001288781.1		c.1480-12T>C		intron	N/A	NP_001275710.1	Q86U25
	TTC8	NM_198309.3		c.1402-12T>C		intron	N/A	NP_938051.1	A0A0C4DGY3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC8	ENST00000380656.7	TSL:2 MANE Select	c.1432-12T>C		intron	N/A	ENSP00000370031.2	Q8TAM2-4
	TTC8	ENST00000338104.10	TSL:1	c.1480-12T>C		intron	N/A	ENSP00000337653.6	A0A0C4DGX9
	TTC8	ENST00000622513.4	TSL:1	c.1402-12T>C		intron	N/A	ENSP00000482721.1	A0A0C4DGY3

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5081 AN: 152156 Hom.: 297 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.00866 AC: 2160 AN: 249516 AF XY: 0.00630

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.00616

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000329

Gnomad OTH exome AF: 0.00477

GnomAD4 exome AF: 0.00339 AC: 4928 AN: 1454654 Hom.: 262 Cov.: 29 AF XY: 0.00291 AC XY: 2108 AN XY: 724162

African (AFR) AF: 0.119 AC: 3959 AN: 33296

American (AMR) AF: 0.00688 AC: 307 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.000163 AC: 14 AN: 86094

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53372

Middle Eastern (MID) AF: 0.00452 AC: 26 AN: 5748

European-Non Finnish (NFE) AF: 0.000185 AC: 205 AN: 1105774

Other (OTH) AF: 0.00691 AC: 415 AN: 60100

GnomAD4 genome AF: 0.0334 AC: 5087 AN: 152274 Hom.: 298 Cov.: 33 AF XY: 0.0317 AC XY: 2363 AN XY: 74464

African (AFR) AF: 0.116 AC: 4821 AN: 41544

American (AMR) AF: 0.0126 AC: 193 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68016

Other (OTH) AF: 0.0189 AC: 40 AN: 2114

Alfa AF: 0.0155 Hom.: 31

Bravo AF: 0.0378

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	Bardet-Biedl syndrome 8 (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.2
DANN	Benign	0.80
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs79747892; hg19: chr14-89343626;