rs796052142

Variant names:

• chr10-95693748-G-T
• rs796052142
• NM_015631.6:c.152C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-95693748-G-T
• chr10-95693748-G-A

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 10P and 1B. PVS1 PM2 BP6

The NM_015631.6(TCTN3):​c.152C>A​(p.Ser51*) variant causes a stop gained 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 Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. S51S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCTN3 NM_015631.6 stop_gained
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.36
• Publications: 1 publications found

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]

TCTN3 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• orofaciodigital syndrome IV

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia
• Joubert syndrome 18

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 10-95693748-G-T is Benign according to our data. Variant chr10-95693748-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 207834.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015631.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN3	NM_015631.6	MANE Select	c.152C>A	p.Ser51*	stop_gained	Exon 1 of 14	NP_056446.4	Q6NUS6-1
	TCTN3	NM_001410982.1		c.152C>A	p.Ser51*	stop_gained	Exon 1 of 13	NP_001397911.1	A0A7P0TB57
	TCTN3	NM_001143973.2		c.152C>A	p.Ser51*	stop_gained	Exon 1 of 10	NP_001137445.1	Q6NUS6-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN3	ENST00000371217.10	TSL:1 MANE Select	c.152C>A	p.Ser51*	stop_gained	Exon 1 of 14	ENSP00000360261.5	Q6NUS6-1
	TCTN3	ENST00000265993.13	TSL:1	c.206C>A	p.Ser69*	stop_gained	Exon 1 of 14	ENSP00000265993.9	A0A0C4DFN5
	TCTN3	ENST00000614499.5	TSL:1	c.206C>A	p.Ser69*	stop_gained	Exon 1 of 14	ENSP00000483364.2	A0A804G9W2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	32
DANN	Uncertain	0.99
Eigen	Benign	0.17
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.016	N
PhyloP100		1.4
Vest4		0.40
ClinPred		0.77	D
GERP RS		3.6
PromoterAI		0.059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=50/150	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs796052142; hg19: chr10-97453505;