NM_144596.4:c.-23C>A

Variant names:

• chr14-88824685-C-A
• rs1001706742
• NM_144596.4:c.-23C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144596.4(TTC8):​c.-23C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TTC8 NM_144596.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 1 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, G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa 51

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

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.-23C>A		5_prime_UTR	Exon 1 of 15	NP_653197.2
	TTC8	NM_001288781.1		c.-23C>A		5_prime_UTR	Exon 2 of 16	NP_001275710.1	Q86U25
	TTC8	NM_198309.3		c.-23C>A		5_prime_UTR	Exon 2 of 15	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.-23C>A		5_prime_UTR	Exon 1 of 15	ENSP00000370031.2	Q8TAM2-4
	TTC8	ENST00000338104.10	TSL:1	c.-23C>A		5_prime_UTR	Exon 1 of 15	ENSP00000337653.6	A0A0C4DGX9
	TTC8	ENST00000622513.4	TSL:1	c.-23C>A		5_prime_UTR	Exon 1 of 14	ENSP00000482721.1	A0A0C4DGY3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 195576 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426122 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 707166

African (AFR) AF: 0.0000305 AC: 1 AN: 32766

American (AMR) AF: 0.00 AC: 0 AN: 40332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25506

East Asian (EAS) AF: 0.00 AC: 0 AN: 38246

South Asian (SAS) AF: 0.00 AC: 0 AN: 82320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4826

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092722

Other (OTH) AF: 0.00 AC: 0 AN: 59000

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.3
DANN	Benign	0.73
PhyloP100		-0.018
PromoterAI		-0.47	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1001706742; hg19: chr14-89291029;