1-230924873-T-A

Position:

• chr1-230924873-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024525.5(TTC13):​c.1689A>T​(p.Arg563Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TTC13 NM_024525.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.998

Genes affected

TTC13 (HGNC:26204): (tetratricopeptide repeat domain 13)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC13	NM_024525.5	c.1689A>T	p.Arg563Ser	missense_variant	14/23	ENST00000366661.9	NP_078801.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC13	ENST00000366661.9	c.1689A>T	p.Arg563Ser	missense_variant	14/23	1	NM_024525.5	ENSP00000355621.4
TTC13	ENST00000366662.8	c.1530A>T	p.Arg510Ser	missense_variant	12/21	1		ENSP00000355622.4
TTC13	ENST00000486879.2	c.-10A>T		upstream_gene_variant		5		ENSP00000428447.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Dec 04, 2024

The c.1689A>T (p.R563S) alteration is located in exon 14 (coding exon 14) of the TTC13 gene. This alteration results from a A to T substitution at nucleotide position 1689, causing the arginine (R) at amino acid position 563 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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.94
MutPred		0.50		Loss of MoRF binding (P = 0.1792);.;
MVP		0.64
MPC		1.0
ClinPred		0.99	D
GERP RS		3.2
Varity_R		0.87
gMVP		0.92

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: chr1-231060619;