11-43401515-G-A

Variant names:

• chr11-43401515-G-A
• NM_018259.6:c.1289G>A

Variant summary

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

The NM_018259.6(TTC17):​c.1289G>A​(p.Arg430His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,162 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TTC17 NM_018259.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.10

Genes affected

TTC17 (HGNC:25596): (tetratricopeptide repeat domain 17) Involved in actin filament polymerization and cilium organization. Located in actin cytoskeleton; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC17	NM_018259.6	c.1289G>A	p.Arg430His	missense_variant	Exon 10 of 24	ENST00000039989.9	NP_060729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC17	ENST00000039989.9	c.1289G>A	p.Arg430His	missense_variant	Exon 10 of 24	1	NM_018259.6	ENSP00000039989.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461162 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726844

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1289G>A (p.R430H) alteration is located in exon 10 (coding exon 10) of the TTC17 gene. This alteration results from a G to A substitution at nucleotide position 1289, causing the arginine (R) at amino acid position 430 to be replaced by a histidine (H). 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	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.049	.;T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.87	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.060	T;D
Sift4G	Uncertain	0.044	D;D
Polyphen		1.0	.;D
Vest4		0.77
MutPred		0.38		Loss of catalytic residue at R430 (P = 0.0612);Loss of catalytic residue at R430 (P = 0.0612);
MVP		0.43
MPC		0.78
ClinPred		0.80	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-43423065; COSMIC: COSV50020918; COSMIC: COSV50020918;