rs118096349

Variant names:

• chr12-110645031-G-T
• rs118096349
• NM_001082538.3:c.1396G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-110645031-G-T
• chr12-110645031-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001082538.3(TCTN1):​c.1396G>T​(p.Gly466Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0232 in 1,614,174 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (37 hom., cov: 32)
  • Exomes 𝑓: 0.024 (542 hom.)
• Consequence: TCTN1 NM_001082538.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.63
• Publications: 15 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045828223).
• BP6: Variant 12-110645031-G-T is Benign according to our data. Variant chr12-110645031-G-T is described in ClinVar as Benign. ClinVar VariationId is 160095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.051 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.1396G>T	p.Gly466Cys	missense	Exon 12 of 15	NP_001076007.1	Q2MV58-2
	TCTN1	NM_001082537.3		c.1396G>T	p.Gly466Cys	missense	Exon 12 of 15	NP_001076006.1	Q2MV58-1
	TCTN1	NM_024549.6		c.1354G>T	p.Gly452Cys	missense	Exon 12 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.1396G>T	p.Gly466Cys	missense	Exon 12 of 15	ENSP00000380779.4	Q2MV58-2
	TCTN1	ENST00000551590.5	TSL:1	c.1396G>T	p.Gly466Cys	missense	Exon 12 of 15	ENSP00000448735.1	Q2MV58-1
	TCTN1	ENST00000397655.7	TSL:1	c.1354G>T	p.Gly452Cys	missense	Exon 12 of 15	ENSP00000380775.3	Q2MV58-3

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2532 AN: 152174 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.00401

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.0569

Gnomad FIN AF: 0.00867

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0236

Gnomad OTH AF: 0.00862

GnomAD2 exomes AF: 0.0214 AC: 5338 AN: 249560 AF XY: 0.0228

Gnomad AFR exome AF: 0.00368

Gnomad AMR exome AF: 0.0141

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.0118

Gnomad FIN exome AF: 0.0110

Gnomad NFE exome AF: 0.0230

Gnomad OTH exome AF: 0.0195

GnomAD4 exome AF: 0.0239 AC: 34883 AN: 1461882 Hom.: 542 Cov.: 30 AF XY: 0.0244 AC XY: 17762 AN XY: 727242

African (AFR) AF: 0.00370 AC: 124 AN: 33480

American (AMR) AF: 0.0143 AC: 641 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 60 AN: 26136

East Asian (EAS) AF: 0.0106 AC: 419 AN: 39700

South Asian (SAS) AF: 0.0505 AC: 4358 AN: 86258

European-Finnish (FIN) AF: 0.0114 AC: 608 AN: 53416

Middle Eastern (MID) AF: 0.00937 AC: 54 AN: 5766

European-Non Finnish (NFE) AF: 0.0247 AC: 27479 AN: 1112010

Other (OTH) AF: 0.0189 AC: 1140 AN: 60392

GnomAD4 genome AF: 0.0166 AC: 2535 AN: 152292 Hom.: 37 Cov.: 32 AF XY: 0.0176 AC XY: 1310 AN XY: 74468

African (AFR) AF: 0.00399 AC: 166 AN: 41566

American (AMR) AF: 0.0184 AC: 281 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5180

South Asian (SAS) AF: 0.0565 AC: 273 AN: 4830

European-Finnish (FIN) AF: 0.00867 AC: 92 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0236 AC: 1605 AN: 68008

Other (OTH) AF: 0.0133 AC: 28 AN: 2110

Alfa AF: 0.0200 Hom.: 53

Bravo AF: 0.0161

TwinsUK AF: 0.0272 AC: 101

ALSPAC AF: 0.0272 AC: 105

ESP6500AA AF: 0.00397 AC: 15

ESP6500EA AF: 0.0211 AC: 173

ExAC AF: 0.0229 AC: 2769

Asia WGS AF: 0.0290 AC: 102 AN: 3478

EpiCase AF: 0.0187

EpiControl AF: 0.0181

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
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.023
Eigen_PC	Benign	0.0073
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0046	T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.6
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.014	D
Sift4G	Benign	0.088	T
Polyphen		1.0	D
Vest4		0.10
MPC		0.70
ClinPred		0.014	T
GERP RS		3.5
Varity_R		0.16
gMVP		0.53
Mutation Taster		=92/8	polymorphism (auto)

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: rs118096349; hg19: chr12-111082836;