11-43405595-A-T

Position:

• chr11-43405595-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018259.6(TTC17):​c.1561A>T​(p.Thr521Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC17 NM_018259.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.86

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]

TTC17 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32540184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC17	NM_018259.6	c.1561A>T	p.Thr521Ser	missense_variant	12/24	ENST00000039989.9	NP_060729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC17	ENST00000039989.9	c.1561A>T	p.Thr521Ser	missense_variant	12/24	1	NM_018259.6	ENSP00000039989.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000378

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

Jul 02, 2024

The c.1561A>T (p.T521S) alteration is located in exon 12 (coding exon 12) of the TTC17 gene. This alteration results from a A to T substitution at nucleotide position 1561, causing the threonine (T) at amino acid position 521 to be replaced by a serine (S). 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	0.30
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	.;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.78	N;N
REVEL	Benign	0.14
Sift	Benign	0.16	T;T
Sift4G	Pathogenic	0.0	D;T
Polyphen		1.0	.;D
Vest4		0.45
MutPred		0.25		Loss of glycosylation at T521 (P = 0.0459);Loss of glycosylation at T521 (P = 0.0459);
MVP		0.31
MPC		0.20
ClinPred		0.55	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.60

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: rs781310767; hg19: chr11-43427145;