14-70672562-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015351.2(TTC9):c.*1407G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,116 control chromosomes in the GnomAD database, including 22,451 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 0.53 (22451 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: TTC9 NM_015351.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

Genes affected

TTC9 (HGNC:20267): (tetratricopeptide repeat domain 9) This gene encodes a protein that contains three tetratricopeptide repeats. The gene has been shown to be hormonally regulated in breast cancer cells and may play a role in cancer cell invasion and metastasis. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC9	NM_015351.2	c.*1407G>T		3_prime_UTR_variant	3/3	ENST00000256367.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC9	ENST00000256367.3	c.*1407G>T		3_prime_UTR_variant	3/3	1	NM_015351.2	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80055 AN: 151998 Hom.: 22423 Cov.: 33

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.505

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.527 AC: 80125 AN: 152116 Hom.: 22451 Cov.: 33 AF XY: 0.520 AC XY: 38687 AN XY: 74356

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.500

Alfa AF: 0.466 Hom.: 23572

Bravo AF: 0.539

Asia WGS AF: 0.477 AC: 1658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	9.1
Dann	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs8688; hg19: chr14-71139279;