rs201913681

Positions:

• chr12-110647730-ATC-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001082538.3(TCTN1):​c.1636-13_1636-12delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00903 in 1,614,162 control chromosomes in the GnomAD database, including 72 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.0069 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0092 (71 hom.)
• Consequence: TCTN1 NM_001082538.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.589

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]

HVCN1 (HGNC:28240): (hydrogen voltage gated channel 1) This gene encodes a voltage-gated protein channel protein expressed more highly in certain cells of the immune system. Phagocytic cells produce superoxide anions which require this channel protein, and in B cells this same process facilitates antibody production. This same channel protein, however, can also regulate functions in other cells including spermatozoa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

TCTN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 12-110647730-ATC-A is Benign according to our data. Variant chr12-110647730-ATC-A is described in ClinVar as [Likely_benign]. Clinvar id is 445373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-110647730-ATC-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00688 (1048/152278) while in subpopulation NFE AF= 0.00945 (643/68028). AF 95% confidence interval is 0.00885. There are 1 homozygotes in gnomad4. There are 508 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 71 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCTN1	NM_001082538.3	c.1636-13_1636-12delCT		intron_variant		ENST00000397659.9	NP_001076007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCTN1	ENST00000397659.9	c.1636-13_1636-12delCT		intron_variant		1	NM_001082538.3	ENSP00000380779.4
TCTN1	ENST00000551590.5	c.1621-13_1621-12delCT		intron_variant		1		ENSP00000448735.1
TCTN1	ENST00000397655.7	c.1579-13_1579-12delCT		intron_variant		1		ENSP00000380775.3
TCTN1	ENST00000397656.8	n.*1254-13_*1254-12delCT		intron_variant		2		ENSP00000380776.4
TCTN1	ENST00000480648.5	n.*897-13_*897-12delCT		intron_variant		5		ENSP00000437196.1
TCTN1	ENST00000495659.6	n.*1379-13_*1379-12delCT		intron_variant		2		ENSP00000436673.2

Frequencies

GnomAD3 genomes AF: 0.00689 AC: 1049 AN: 152160 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00799

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00434

Gnomad FIN AF: 0.0171

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00945

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00749 AC: 1869 AN: 249568 Hom.: 10 AF XY: 0.00758 AC XY: 1027 AN XY: 135402

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00475

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00454

Gnomad FIN exome AF: 0.0189

Gnomad NFE exome AF: 0.00932

Gnomad OTH exome AF: 0.00990

GnomAD4 exome AF: 0.00925 AC: 13521 AN: 1461884 Hom.: 71 AF XY: 0.00915 AC XY: 6657 AN XY: 727246

Gnomad4 AFR exome AF: 0.00116

Gnomad4 AMR exome AF: 0.00510

Gnomad4 ASJ exome AF: 0.00145

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00547

Gnomad4 FIN exome AF: 0.0182

Gnomad4 NFE exome AF: 0.0102

Gnomad4 OTH exome AF: 0.00654

GnomAD4 genome AF: 0.00688 AC: 1048 AN: 152278 Hom.: 1 Cov.: 32 AF XY: 0.00682 AC XY: 508 AN XY: 74464

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.00791

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00434

Gnomad4 FIN AF: 0.0171

Gnomad4 NFE AF: 0.00945

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00676 Hom.: 1

Bravo AF: 0.00602

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 23, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs201913681; hg19: chr12-111085535;