NM_015351.2:c.*1407G>T

Variant names:

• chr14-70672562-G-T
• rs8688
• NM_015351.2:c.*1407G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TTC9	NM_015351.2	c.*1407G>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000256367.3	NP_056166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC9	ENST00000256367.3	c.*1407G>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_015351.2	ENSP00000256367.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.725 AC: 30102 AN: 41506

American (AMR) AF: 0.447 AC: 6834 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1740 AN: 3472

East Asian (EAS) AF: 0.566 AC: 2930 AN: 5180

South Asian (SAS) AF: 0.439 AC: 2119 AN: 4828

European-Finnish (FIN) AF: 0.376 AC: 3978 AN: 10572

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30791 AN: 67966

Other (OTH) AF: 0.500 AC: 1058 AN: 2116

Alfa AF: 0.475 Hom.: 33664

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
PhyloP100		0.066
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: rs8688; hg19: chr14-71139279;