12-110614164-C-G

Position:

• chr12-110614164-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001082538.3(TCTN1):​c.-19C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,254 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TCTN1 NM_001082538.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521

Genes affected

TCTN1 (HGNC:26113): (tectonic family member 1) This gene encodes a member of a family of secreted and transmembrane proteins. The orthologous gene in mouse functions downstream of smoothened and rab23 to modulate hedgehog signal transduction. This protein is a component of the tectonic-like complex, which forms a barrier between the ciliary axoneme and the basal body. A mutation in this gene was found in a family with Joubert syndrome-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCTN1	NM_001082538.3	c.-19C>G		5_prime_UTR_premature_start_codon_gain_variant	1/15	ENST00000397659.9	NP_001076007.1
TCTN1	NM_001082538.3	c.-19C>G		5_prime_UTR_variant	1/15	ENST00000397659.9	NP_001076007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCTN1	ENST00000397659	c.-19C>G		5_prime_UTR_premature_start_codon_gain_variant	1/15	1	NM_001082538.3	ENSP00000380779.4
TCTN1	ENST00000551590	c.-19C>G		5_prime_UTR_premature_start_codon_gain_variant	1/15	1		ENSP00000448735.1
TCTN1	ENST00000397655	c.-19C>G		5_prime_UTR_premature_start_codon_gain_variant	1/15	1		ENSP00000380775.3
TCTN1	ENST00000397659	c.-19C>G		5_prime_UTR_variant	1/15	1	NM_001082538.3	ENSP00000380779.4
TCTN1	ENST00000551590	c.-19C>G		5_prime_UTR_variant	1/15	1		ENSP00000448735.1
TCTN1	ENST00000397655	c.-19C>G		5_prime_UTR_variant	1/15	1		ENSP00000380775.3
TCTN1	ENST00000397656.8	n.-19C>G		5_prime_UTR_premature_start_codon_gain_variant	1/16	2		ENSP00000380776.4
TCTN1	ENST00000495659.6	n.-19C>G		5_prime_UTR_premature_start_codon_gain_variant	1/15	2		ENSP00000436673.2
TCTN1	ENST00000397656.8	n.-19C>G		non_coding_transcript_exon_variant	1/16	2		ENSP00000380776.4
TCTN1	ENST00000495659.6	n.-19C>G		non_coding_transcript_exon_variant	1/15	2		ENSP00000436673.2
TCTN1	ENST00000397656.8	n.-19C>G		5_prime_UTR_variant	1/16	2		ENSP00000380776.4
TCTN1	ENST00000495659.6	n.-19C>G		5_prime_UTR_variant	1/15	2		ENSP00000436673.2
TCTN1	ENST00000480648.5	n.-19C>G		upstream_gene_variant		5		ENSP00000437196.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152254 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74392

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.41

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: rs773061089; hg19: chr12-111051969;