rs201913681

Variant names:

• chr12-110647730-ATC-A
• rs201913681
• NM_001082538.3:c.1636-13_1636-12delCT

Variant summary

Our verdict is Benign. The variant received -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
• 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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 445373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 71 AR gene

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.1636-13_1636-12delCT		intron	N/A	NP_001076007.1
	TCTN1	NM_001082537.3		c.1621-13_1621-12delCT		intron	N/A	NP_001076006.1
	TCTN1	NM_024549.6		c.1579-13_1579-12delCT		intron	N/A	NP_078825.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN1	ENST00000397659.9	TSL:1 MANE Select	c.1636-13_1636-12delCT		intron	N/A	ENSP00000380779.4
	TCTN1	ENST00000551590.5	TSL:1	c.1621-13_1621-12delCT		intron	N/A	ENSP00000448735.1
	TCTN1	ENST00000397655.7	TSL:1	c.1579-13_1579-12delCT		intron	N/A	ENSP00000380775.3

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

GnomAD2 exomes AF: 0.00749 AC: 1869 AN: 249568 AF XY: 0.00758

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 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

African (AFR) AF: 0.00116 AC: 39 AN: 33480

American (AMR) AF: 0.00510 AC: 228 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00145 AC: 38 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00547 AC: 472 AN: 86256

European-Finnish (FIN) AF: 0.0182 AC: 971 AN: 53418

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.0102 AC: 11367 AN: 1112006

Other (OTH) AF: 0.00654 AC: 395 AN: 60396

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

African (AFR) AF: 0.00164 AC: 68 AN: 41540

American (AMR) AF: 0.00791 AC: 121 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00434 AC: 21 AN: 4834

European-Finnish (FIN) AF: 0.0171 AC: 181 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00945 AC: 643 AN: 68028

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00676 Hom.: 1

Bravo AF: 0.00602

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Meckel-Gruber syndrome;C0431399:Joubert syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.59
BranchPoint Hunter		1.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201913681; hg19: chr12-111085535;