chr12-110632544-G-GATA

Variant names:

• chr12-110632544-G-GATA
• rs797046038
• NM_001082538.3:c.702_704dupTAA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001082538.3(TCTN1):​c.702_704dupTAA​(p.Asn235dup) variant causes a disruptive inframe insertion change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N235N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCTN1 NM_001082538.3 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.66
• Publications: 2 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001082538.3. Strenght limited to Supporting due to length of the change: 1aa.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN1	NM_001082538.3	MANE Select	c.702_704dupTAA	p.Asn235dup	disruptive_inframe_insertion	Exon 5 of 15	NP_001076007.1
	TCTN1	NM_001082537.3		c.702_704dupTAA	p.Asn235dup	disruptive_inframe_insertion	Exon 5 of 15	NP_001076006.1
	TCTN1	NM_024549.6		c.702_704dupTAA	p.Asn235dup	disruptive_inframe_insertion	Exon 5 of 15	NP_078825.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN1	ENST00000397659.9	TSL:1 MANE Select	c.702_704dupTAA	p.Asn235dup	disruptive_inframe_insertion	Exon 5 of 15	ENSP00000380779.4
	TCTN1	ENST00000551590.5	TSL:1	c.702_704dupTAA	p.Asn235dup	disruptive_inframe_insertion	Exon 5 of 15	ENSP00000448735.1
	TCTN1	ENST00000397655.7	TSL:1	c.702_704dupTAA	p.Asn235dup	disruptive_inframe_insertion	Exon 5 of 15	ENSP00000380775.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000753 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs797046038; hg19: chr12-111070349;