rs1968699

Variant names:

• chr15-99171551-C-T
• rs1968699
• NM_001288615.3:c.865+3499G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288615.3(TTC23):​c.865+3499G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 144,162 control chromosomes in the GnomAD database, including 671 homozygotes. 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: 𝑓 0.082 (671 hom., cov: 30)
• Consequence: TTC23 NM_001288615.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 3 publications found

Genes affected

TTC23 (HGNC:25730): (tetratricopeptide repeat domain 23) Predicted to be involved in positive regulation of smoothened signaling pathway. Predicted to be located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288615.3. 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
	TTC23	NM_001288615.3	MANE Select	c.865+3499G>A		intron	N/A	NP_001275544.1	Q5W5X9-1
	TTC23	NM_001288616.3		c.865+3499G>A		intron	N/A	NP_001275545.1	Q5W5X9-1
	TTC23	NM_001353869.2		c.865+3499G>A		intron	N/A	NP_001340798.1	Q5W5X9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC23	ENST00000394132.7	TSL:1 MANE Select	c.865+3499G>A		intron	N/A	ENSP00000377690.2	Q5W5X9-1
	TTC23	ENST00000459771.5	TSL:1	n.865+3499G>A		intron	N/A	ENSP00000433162.1	Q5W5X9-3
	TTC23	ENST00000961241.1		c.865+3499G>A		intron	N/A	ENSP00000631300.1

Frequencies

GnomAD3 genomes AF: 0.0816 AC: 11760 AN: 144084 Hom.: 662 Cov.: 30

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0391

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.0451

Gnomad FIN AF: 0.0549

Gnomad MID AF: 0.0473

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.0615

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0819 AC: 11802 AN: 144162 Hom.: 671 Cov.: 30 AF XY: 0.0816 AC XY: 5668 AN XY: 69458

African (AFR) AF: 0.162 AC: 6351 AN: 39240

American (AMR) AF: 0.0372 AC: 522 AN: 14022

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 209 AN: 3418

East Asian (EAS) AF: 0.0167 AC: 78 AN: 4674

South Asian (SAS) AF: 0.0450 AC: 205 AN: 4554

European-Finnish (FIN) AF: 0.0549 AC: 456 AN: 8312

Middle Eastern (MID) AF: 0.0547 AC: 15 AN: 274

European-Non Finnish (NFE) AF: 0.0570 AC: 3808 AN: 66756

Other (OTH) AF: 0.0610 AC: 123 AN: 2018

Alfa AF: 0.0671 Hom.: 279

Bravo AF: 0.0843

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.83
DANN	Benign	0.63
PhyloP100		-0.32
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: rs1968699; hg19: chr15-99711756;