14-70642251-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015351.2(TTC9):c.122G>A(p.Arg41Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC9 NM_015351.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1431548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC9	NM_015351.2	c.122G>A	p.Arg41Lys	missense_variant	1/3	ENST00000256367.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC9	ENST00000256367.3	c.122G>A	p.Arg41Lys	missense_variant	1/3	1	NM_015351.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.122G>A (p.R41K) alteration is located in exon 1 (coding exon 1) of the TTC9 gene. This alteration results from a G to A substitution at nucleotide position 122, causing the arginine (R) at amino acid position 41 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	19
Dann	Uncertain	0.97
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	0.82	D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.072
Sift	Benign	0.18	T
Sift4G	Benign	0.23	T
Polyphen		0.0040	B
Vest4		0.10
MutPred		0.40		Gain of catalytic residue at G36 (P = 0);
MVP		0.20
MPC		0.96
ClinPred		0.37	T
GERP RS		3.3
Varity_R		0.17
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-71108968;