rs16940927

Variant names:

• chr12-110640433-C-T
• rs16940927
• NM_001082538.3:c.894C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-110640433-C-T
• chr12-110640433-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001082538.3(TCTN1):​c.894C>T​(p.Leu298Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,614,132 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (89 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (77 hom.)
• Consequence: TCTN1 NM_001082538.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.27
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-110640433-C-T is Benign according to our data. Variant chr12-110640433-C-T is described in ClinVar as Benign. ClinVar VariationId is 160099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0596 is higher than 0.05.

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.894C>T	p.Leu298Leu	synonymous	Exon 8 of 15	NP_001076007.1	Q2MV58-2
	TCTN1	NM_001082537.3		c.894C>T	p.Leu298Leu	synonymous	Exon 8 of 15	NP_001076006.1	Q2MV58-1
	TCTN1	NM_024549.6		c.852C>T	p.Leu284Leu	synonymous	Exon 8 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.894C>T	p.Leu298Leu	synonymous	Exon 8 of 15	ENSP00000380779.4	Q2MV58-2
	TCTN1	ENST00000551590.5	TSL:1	c.894C>T	p.Leu298Leu	synonymous	Exon 8 of 15	ENSP00000448735.1	Q2MV58-1
	TCTN1	ENST00000397655.7	TSL:1	c.852C>T	p.Leu284Leu	synonymous	Exon 8 of 15	ENSP00000380775.3	Q2MV58-3

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2711 AN: 152126 Hom.: 90 Cov.: 32

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00498 AC: 1243 AN: 249570 AF XY: 0.00383

Gnomad AFR exome AF: 0.0667

Gnomad AMR exome AF: 0.00434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.00412

GnomAD4 exome AF: 0.00197 AC: 2873 AN: 1461886 Hom.: 77 Cov.: 31 AF XY: 0.00168 AC XY: 1220 AN XY: 727242

African (AFR) AF: 0.0636 AC: 2129 AN: 33478

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86252

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00520 AC: 30 AN: 5768

European-Non Finnish (NFE) AF: 0.000205 AC: 228 AN: 1112012

Other (OTH) AF: 0.00409 AC: 247 AN: 60396

GnomAD4 genome AF: 0.0178 AC: 2717 AN: 152246 Hom.: 89 Cov.: 32 AF XY: 0.0172 AC XY: 1280 AN XY: 74454

African (AFR) AF: 0.0616 AC: 2559 AN: 41530

American (AMR) AF: 0.00700 AC: 107 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68022

Other (OTH) AF: 0.0119 AC: 25 AN: 2108

Alfa AF: 0.00572 Hom.: 22

Bravo AF: 0.0207

Asia WGS AF: 0.00289 AC: 11 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Joubert syndrome 13 (1)
-	-	1	Meckel-Gruber syndrome;C5979921:Joubert syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.32
DANN	Benign	0.85
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs16940927; hg19: chr12-111078238;