ENST00000555057.5:n.*1193G>A

Variant names:

• chr14-88877648-G-A
• rs1048190
• ENST00000555057.5:n.*1193G>A

Variant summary

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

The ENST00000555057.5(TTC8):​n.*1193G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 345,966 control chromosomes in the GnomAD database, including 10,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3829 hom., cov: 32)
  • Exomes 𝑓: 0.25 (6330 hom.)
• Consequence: TTC8 ENST00000555057.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.759
• Publications: 13 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: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa 51

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.84).
• BP6: Variant 14-88877648-G-A is Benign according to our data. Variant chr14-88877648-G-A is described in ClinVar as Benign. ClinVar VariationId is 314807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000555057.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC8	NM_144596.4	MANE Select	c.*238G>A		3_prime_UTR	Exon 15 of 15	NP_653197.2
	TTC8	NR_159362.2		n.1873G>A		non_coding_transcript_exon	Exon 15 of 15
	TTC8	NM_001288781.1		c.*238G>A		3_prime_UTR	Exon 16 of 16	NP_001275710.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC8	ENST00000555057.5	TSL:1	n.*1193G>A		non_coding_transcript_exon	Exon 13 of 13	ENSP00000450951.1
	TTC8	ENST00000380656.7	TSL:2 MANE Select	c.*238G>A		3_prime_UTR	Exon 15 of 15	ENSP00000370031.2
	TTC8	ENST00000338104.10	TSL:1	c.*238G>A		3_prime_UTR	Exon 15 of 15	ENSP00000337653.6

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31745 AN: 152030 Hom.: 3820 Cov.: 32

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.249 AC: 48299 AN: 193818 Hom.: 6330 Cov.: 0 AF XY: 0.247 AC XY: 25403 AN XY: 102798

African (AFR) AF: 0.0827 AC: 491 AN: 5934

American (AMR) AF: 0.186 AC: 1539 AN: 8262

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 1396 AN: 6310

East Asian (EAS) AF: 0.320 AC: 4289 AN: 13406

South Asian (SAS) AF: 0.204 AC: 3728 AN: 18316

European-Finnish (FIN) AF: 0.251 AC: 2111 AN: 8420

Middle Eastern (MID) AF: 0.153 AC: 133 AN: 870

European-Non Finnish (NFE) AF: 0.264 AC: 31845 AN: 120666

Other (OTH) AF: 0.238 AC: 2767 AN: 11634

GnomAD4 genome AF: 0.209 AC: 31779 AN: 152148 Hom.: 3829 Cov.: 32 AF XY: 0.207 AC XY: 15412 AN XY: 74382

African (AFR) AF: 0.0926 AC: 3845 AN: 41526

American (AMR) AF: 0.204 AC: 3114 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 768 AN: 3468

East Asian (EAS) AF: 0.317 AC: 1639 AN: 5174

South Asian (SAS) AF: 0.224 AC: 1083 AN: 4826

European-Finnish (FIN) AF: 0.243 AC: 2568 AN: 10588

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18051 AN: 67978

Other (OTH) AF: 0.190 AC: 401 AN: 2114

Alfa AF: 0.221 Hom.: 841

Bravo AF: 0.201

Asia WGS AF: 0.233 AC: 810 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Bardet-Biedl syndrome 8 (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.19
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1048190; hg19: chr14-89343992;