chr12-110628757-TAA-T

Variant names:

• chr12-110628757-TAA-T
• rs10577377
• NM_001082538.3:c.473-5_473-4delAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001082538.3(TCTN1):​c.473-5_473-4delAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,434,288 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TCTN1 NM_001082538.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.473-5_473-4delAA		splice_region intron	N/A	NP_001076007.1	Q2MV58-2
	TCTN1	NM_001082537.3		c.473-5_473-4delAA		splice_region intron	N/A	NP_001076006.1	Q2MV58-1
	TCTN1	NM_024549.6		c.473-5_473-4delAA		splice_region 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.473-9_473-8delAA		splice_region intron	N/A	ENSP00000380779.4	Q2MV58-2
	TCTN1	ENST00000551590.5	TSL:1	c.473-9_473-8delAA		splice_region intron	N/A	ENSP00000448735.1	Q2MV58-1
	TCTN1	ENST00000397655.7	TSL:1	c.473-9_473-8delAA		splice_region intron	N/A	ENSP00000380775.3	Q2MV58-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000821 AC: 2 AN: 243572 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000587

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1434288 Hom.: 0 AF XY: 0.00000420 AC XY: 3 AN XY: 715130

African (AFR) AF: 0.00 AC: 0 AN: 32906

American (AMR) AF: 0.0000674 AC: 3 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25958

East Asian (EAS) AF: 0.00 AC: 0 AN: 39454

South Asian (SAS) AF: 0.00 AC: 0 AN: 85478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5538

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090594

Other (OTH) AF: 0.00 AC: 0 AN: 59530

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.57

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: rs10577377; hg19: chr12-111066562;