1-230924919-T-G

Position:

• chr1-230924919-T-G

Variant summary

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

The NM_024525.5(TTC13):​c.1643A>C​(p.Asn548Thr) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TTC13 NM_024525.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.19

Genes affected

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

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=0.38322276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC13	NM_024525.5	c.1643A>C	p.Asn548Thr	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.1643A>C	p.Asn548Thr	missense_variant	14/23	1	NM_024525.5	ENSP00000355621	P1
TTC13	ENST00000366662.8	c.1484A>C	p.Asn495Thr	missense_variant	12/21	1		ENSP00000355622

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 20, 2023

The c.1643A>C (p.N548T) alteration is located in exon 14 (coding exon 14) of the TTC13 gene. This alteration results from a A to C substitution at nucleotide position 1643, causing the asparagine (N) at amino acid position 548 to be replaced by a threonine (T). 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	0.22
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	T;.
Eigen	Benign	0.0024
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.68	N;N
REVEL	Benign	0.12
Sift	Benign	0.030	D;D
Sift4G	Benign	0.14	T;T
Polyphen		0.38	B;P
Vest4		0.56
MutPred		0.59		Loss of loop (P = 0.1242);.;
MVP		0.15
MPC		0.32
ClinPred		0.77	D
GERP RS		4.3
Varity_R		0.14
gMVP		0.69

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: chr1-231060665;