rs538932401

Variant names:

• chr12-110614137-G-A
• rs538932401
• NM_001082538.3:c.-46G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-110614137-G-A
• chr12-110614137-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001082538.3(TCTN1):​c.-46G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00000288 in 1,388,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: TCTN1 NM_001082538.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCTN1	NM_001082538.3	c.-46G>A		5_prime_UTR_variant	Exon 1 of 15	ENST00000397659.9	NP_001076007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCTN1	ENST00000397659	c.-46G>A		5_prime_UTR_variant	Exon 1 of 15	1	NM_001082538.3	ENSP00000380779.4
TCTN1	ENST00000551590	c.-46G>A		5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000448735.1
TCTN1	ENST00000397655	c.-46G>A		5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000380775.3
TCTN1	ENST00000397656.8	n.-46G>A		non_coding_transcript_exon_variant	Exon 1 of 16	2		ENSP00000380776.4
TCTN1	ENST00000495659.6	n.-46G>A		non_coding_transcript_exon_variant	Exon 1 of 15	2		ENSP00000436673.2
TCTN1	ENST00000397656.8	n.-46G>A		5_prime_UTR_variant	Exon 1 of 16	2		ENSP00000380776.4
TCTN1	ENST00000495659.6	n.-46G>A		5_prime_UTR_variant	Exon 1 of 15	2		ENSP00000436673.2
TCTN1	ENST00000480648.5	n.-46G>A		upstream_gene_variant		5		ENSP00000437196.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000288 AC: 4 AN: 1388824 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 684612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000279

Gnomad4 OTH exome AF: 0.0000174

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs538932401; hg19: chr12-111051942;