rs779892252

Variant names:

• chr12-110614239-C-A
• rs779892252
• NM_001082538.3:c.57C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-110614239-C-A
• chr12-110614239-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001082538.3(TCTN1):​c.57C>A​(p.Ser19Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,050 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TCTN1 NM_001082538.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=-3.49 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCTN1	NM_001082538.3	c.57C>A	p.Ser19Ser	synonymous_variant	Exon 1 of 15	ENST00000397659.9	NP_001076007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCTN1	ENST00000397659.9	c.57C>A	p.Ser19Ser	synonymous_variant	Exon 1 of 15	1	NM_001082538.3	ENSP00000380779.4
TCTN1	ENST00000551590.5	c.57C>A	p.Ser19Ser	synonymous_variant	Exon 1 of 15	1		ENSP00000448735.1
TCTN1	ENST00000397655.7	c.57C>A	p.Ser19Ser	synonymous_variant	Exon 1 of 15	1		ENSP00000380775.3
TCTN1	ENST00000397656.8	n.57C>A		non_coding_transcript_exon_variant	Exon 1 of 16	2		ENSP00000380776.4
TCTN1	ENST00000480648.5	n.57C>A		non_coding_transcript_exon_variant	Exon 1 of 16	5		ENSP00000437196.1
TCTN1	ENST00000495659.6	n.57C>A		non_coding_transcript_exon_variant	Exon 1 of 15	2		ENSP00000436673.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000487 AC: 1 AN: 205272 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 112350

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000112

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439050 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 713782

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: 9.08e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000244 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	1.4
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs779892252; hg19: chr12-111052044;