chr12-110614203-G-C

Variant names:

• chr12-110614203-G-C
• rs760813360
• NM_001082538.3:c.21G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001082538.3(TCTN1):​c.21G>C​(p.Pro7Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,232 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. Synonymous variant affecting the same amino acid position (i.e. P7P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TCTN1 NM_001082538.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• Publications: 0 publications found

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]

TCTN1 Gene-Disease associations (from GenCC):

• Joubert syndrome 13

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=0.396 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082538.3. 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
	TCTN1	NM_001082538.3	MANE Select	c.21G>C	p.Pro7Pro	synonymous	Exon 1 of 15	NP_001076007.1	Q2MV58-2
	TCTN1	NM_001082537.3		c.21G>C	p.Pro7Pro	synonymous	Exon 1 of 15	NP_001076006.1	Q2MV58-1
	TCTN1	NM_024549.6		c.21G>C	p.Pro7Pro	synonymous	Exon 1 of 15	NP_078825.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN1	ENST00000397659.9	TSL:1 MANE Select	c.21G>C	p.Pro7Pro	synonymous	Exon 1 of 15	ENSP00000380779.4	Q2MV58-2
	TCTN1	ENST00000551590.5	TSL:1	c.21G>C	p.Pro7Pro	synonymous	Exon 1 of 15	ENSP00000448735.1	Q2MV58-1
	TCTN1	ENST00000397655.7	TSL:1	c.21G>C	p.Pro7Pro	synonymous	Exon 1 of 15	ENSP00000380775.3	Q2MV58-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152232 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 180404 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1421518 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 703564

African (AFR) AF: 0.00 AC: 0 AN: 32934

American (AMR) AF: 0.00 AC: 0 AN: 38512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25324

East Asian (EAS) AF: 0.00 AC: 0 AN: 38072

South Asian (SAS) AF: 0.00 AC: 0 AN: 81296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092710

Other (OTH) AF: 0.00 AC: 0 AN: 58784

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152232 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74372

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.7
DANN	Benign	0.61
PhyloP100		0.40
PromoterAI		-0.018	Neutral

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: rs760813360; hg19: chr12-111052008;