10-95664092-C-A

Variant summary

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

The NM_015631.6(TCTN3):c.1799G>T(p.Gly600Val) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TCTN3 NM_015631.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.227

Genes affected

TCTN3 (HGNC:24519): (tectonic family member 3) This gene encodes a member of the tectonic gene family which functions in Hedgehog signal transduction and development of the neural tube. Mutations in this gene have been associated with Orofaciodigital Syndrome IV and Joubert Syndrom 18. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2012]

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=0.2965682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCTN3	NM_015631.6	c.1799G>T	p.Gly600Val	missense_variant	14/14	ENST00000371217.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCTN3	ENST00000371217.10	c.1799G>T	p.Gly600Val	missense_variant	14/14	1	NM_015631.6	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.1799G>T (p.G600V) alteration is located in exon 14 (coding exon 14) of the TCTN3 gene. This alteration results from a G to T substitution at nucleotide position 1799, causing the glycine (G) at amino acid position 600 to be replaced by a valine (V). 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	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0043	T;T;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.58	T;.;T;T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.0	M;M;.;.
MutationTaster	Benign	0.79	D;D;D
PrimateAI	Benign	0.31	T
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		0.83	P;P;.;.
Vest4		0.48
MutPred		0.50		Loss of loop (P = 0.0145);Loss of loop (P = 0.0145);.;.;
MVP		0.42
MPC		0.58
ClinPred		0.66	D
GERP RS		4.0
Varity_R		0.061
gMVP		0.62

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: rs2097923872; hg19: chr10-97423849;