3-180603109-ATT-AT

Variant names:

• chr3-180603109-AT-A
• rs557781816
• NM_133462.4:c.287-3delT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_133462.4(TTC14):​c.287-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 863,730 control chromosomes in the GnomAD database, including 2 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 32)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: TTC14 NM_133462.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

Genes affected

TTC14 (HGNC:24697): (tetratricopeptide repeat domain 14) Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Apr 2022]

CCDC39 (HGNC:25244): (coiled-coil domain 39 molecular ruler complex subunit) The protein encoded by this gene is involved in the motility of cilia and flagella. The encoded protein is essential for the assembly of dynein regulatory and inner dynein arm complexes, which regulate ciliary beat. Defects in this gene are a cause of primary ciliary dyskinesia type 14 (CILD14). [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC14	NM_133462.4	c.287-3delT		splice_region_variant, intron_variant	Intron 2 of 11	ENST00000296015.9	NP_597719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC14	ENST00000296015.9	c.287-14delT		intron_variant	Intron 2 of 11	1	NM_133462.4	ENSP00000296015.4

Frequencies

GnomAD3 genomes AF: 0.00121 AC: 178 AN: 147348 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000680

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000287

Gnomad OTH AF: 0.00150

GnomAD4 exome AF: 0.0418 AC: 29957 AN: 716320 Hom.: 0 Cov.: 26 AF XY: 0.0429 AC XY: 15304 AN XY: 356552

Gnomad4 AFR exome AF: 0.0437

Gnomad4 AMR exome AF: 0.0695

Gnomad4 ASJ exome AF: 0.0639

Gnomad4 EAS exome AF: 0.0471

Gnomad4 SAS exome AF: 0.0617

Gnomad4 FIN exome AF: 0.0497

Gnomad4 NFE exome AF: 0.0380

Gnomad4 OTH exome AF: 0.0439

GnomAD4 genome AF: 0.00121 AC: 178 AN: 147410 Hom.: 2 Cov.: 32 AF XY: 0.00114 AC XY: 82 AN XY: 71796

Gnomad4 AFR AF: 0.00316

Gnomad4 AMR AF: 0.000679

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000215

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.000287

Gnomad4 OTH AF: 0.00149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs557781816; hg19: chr3-180320897;