rs201293727

Variant names:

• chr12-110634661-G-T
• rs201293727
• NM_001082538.3:c.713-9G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001082538.3(TCTN1):​c.713-9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,590,704 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000091 (1 hom.)
• Consequence: TCTN1 NM_001082538.3 intron
• Scores: Splicing: ADA: 0.0005778
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.777
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 12-110634661-G-T is Benign according to our data. Variant chr12-110634661-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 530909.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00023 (35/152160) while in subpopulation AMR AF = 0.000916 (14/15278). AF 95% confidence interval is 0.000553. There are 0 homozygotes in GnomAd4. There are 18 alleles in the male GnomAd4 subpopulation. Median coverage is 32. 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.713-9G>T		intron	N/A	NP_001076007.1
	TCTN1	NM_001082537.3		c.713-9G>T		intron	N/A	NP_001076006.1
	TCTN1	NM_024549.6		c.780+198G>T		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.713-9G>T		intron	N/A	ENSP00000380779.4
	TCTN1	ENST00000551590.5	TSL:1	c.713-9G>T		intron	N/A	ENSP00000448735.1
	TCTN1	ENST00000397655.7	TSL:1	c.780+198G>T		intron	N/A	ENSP00000380775.3

Frequencies

GnomAD3 genomes AF: 0.000224 AC: 34 AN: 152042 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000918

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000116 AC: 26 AN: 224310 AF XY: 0.0000991

Gnomad AFR exome AF: 0.000216

Gnomad AMR exome AF: 0.000444

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000241

Gnomad NFE exome AF: 0.0000199

Gnomad OTH exome AF: 0.000362

GnomAD4 exome AF: 0.0000911 AC: 131 AN: 1438544 Hom.: 1 Cov.: 29 AF XY: 0.0000911 AC XY: 65 AN XY: 713778

African (AFR) AF: 0.00134 AC: 44 AN: 32926

American (AMR) AF: 0.000429 AC: 18 AN: 41928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25422

East Asian (EAS) AF: 0.00 AC: 0 AN: 39518

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81762

European-Finnish (FIN) AF: 0.000228 AC: 12 AN: 52640

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5714

European-Non Finnish (NFE) AF: 0.0000346 AC: 38 AN: 1099114

Other (OTH) AF: 0.000202 AC: 12 AN: 59520

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74372

African (AFR) AF: 0.000410 AC: 17 AN: 41508

American (AMR) AF: 0.000916 AC: 14 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.000155 Hom.: 0

Bravo AF: 0.000280

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Meckel-Gruber syndrome;C0431399:Joubert syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00058
dbscSNV1_RF	Benign	0.13
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: rs201293727; hg19: chr12-111072466;