12-110628749-G-GT

Variant names:

• chr12-110628749-G-GT
• rs771463400
• NM_001082538.3:c.473-10dupT

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The NM_001082538.3(TCTN1):​c.473-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,579,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: TCTN1 NM_001082538.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.239
• 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 -12 ACMG points.

• BP6: Variant 12-110628749-G-GT is Benign according to our data. Variant chr12-110628749-G-GT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1168485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00022 (314/1428052) while in subpopulation MID AF = 0.000739 (4/5414). AF 95% confidence interval is 0.000251. There are 0 homozygotes in GnomAdExome4. There are 148 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.

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.473-10dupT		intron	N/A	NP_001076007.1	Q2MV58-2
	TCTN1	NM_001082537.3		c.473-10dupT		intron	N/A	NP_001076006.1	Q2MV58-1
	TCTN1	NM_024549.6		c.473-10dupT		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.473-18_473-17insT		intron	N/A	ENSP00000380779.4	Q2MV58-2
	TCTN1	ENST00000551590.5	TSL:1	c.473-18_473-17insT		intron	N/A	ENSP00000448735.1	Q2MV58-1
	TCTN1	ENST00000397655.7	TSL:1	c.473-18_473-17insT		intron	N/A	ENSP00000380775.3	Q2MV58-3

Frequencies

GnomAD3 genomes AF: 0.0000923 AC: 14 AN: 151704 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000940 AC: 22 AN: 234146 AF XY: 0.0000783

Gnomad AFR exome AF: 0.0000673

Gnomad AMR exome AF: 0.0000921

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000576

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000122

Gnomad OTH exome AF: 0.000345

GnomAD4 exome AF: 0.000220 AC: 314 AN: 1428052 Hom.: 0 Cov.: 29 AF XY: 0.000208 AC XY: 148 AN XY: 712180

African (AFR) AF: 0.0000611 AC: 2 AN: 32716

American (AMR) AF: 0.0000452 AC: 2 AN: 44284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.0000508 AC: 2 AN: 39374

South Asian (SAS) AF: 0.0000940 AC: 8 AN: 85126

European-Finnish (FIN) AF: 0.0000407 AC: 2 AN: 49118

Middle Eastern (MID) AF: 0.000739 AC: 4 AN: 5414

European-Non Finnish (NFE) AF: 0.000256 AC: 278 AN: 1086850

Other (OTH) AF: 0.000270 AC: 16 AN: 59314

GnomAD4 genome AF: 0.0000922 AC: 14 AN: 151820 Hom.: 0 Cov.: 32 AF XY: 0.0000674 AC XY: 5 AN XY: 74214

African (AFR) AF: 0.0000724 AC: 3 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15138

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67904

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.0000868 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Meckel-Gruber syndrome;C5979921:Joubert syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24

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: rs771463400; hg19: chr12-111066554; COSMIC: COSV66542077; COSMIC: COSV66542077;