NM_015351.2:c.407-1522G>A

Variant names:

• chr14-70666042-G-A
• rs1205233
• NM_015351.2:c.407-1522G>A

Variant summary

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

The NM_015351.2(TTC9):​c.407-1522G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,636 control chromosomes in the GnomAD database, including 20,109 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 0.48 (20109 hom., cov: 30)
• Consequence: TTC9 NM_015351.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC9	NM_015351.2	c.407-1522G>A		intron_variant	Intron 1 of 2	ENST00000256367.3	NP_056166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC9	ENST00000256367.3	c.407-1522G>A		intron_variant	Intron 1 of 2	1	NM_015351.2	ENSP00000256367.2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73180 AN: 151518 Hom.: 20063 Cov.: 30

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.483 AC: 73270 AN: 151636 Hom.: 20109 Cov.: 30 AF XY: 0.477 AC XY: 35297 AN XY: 74072

African (AFR) AF: 0.752 AC: 31059 AN: 41322

American (AMR) AF: 0.378 AC: 5757 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1529 AN: 3468

East Asian (EAS) AF: 0.631 AC: 3252 AN: 5152

South Asian (SAS) AF: 0.424 AC: 2026 AN: 4780

European-Finnish (FIN) AF: 0.296 AC: 3113 AN: 10502

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

European-Non Finnish (NFE) AF: 0.368 AC: 25002 AN: 67896

Other (OTH) AF: 0.457 AC: 958 AN: 2094

Alfa AF: 0.405 Hom.: 17579

Bravo AF: 0.501

Asia WGS AF: 0.505 AC: 1753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.55
PhyloP100		-0.36
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: rs1205233; hg19: chr14-71132759;