10-95663951-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015631.6(TCTN3):c.*116G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 779,128 control chromosomes in the GnomAD database, including 36,691 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6218 hom., cov: 32)
  • Exomes 𝑓: 0.30 (30473 hom.)
• Consequence: TCTN3 NM_015631.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.290

Genes affected

TCTN3 (HGNC:24519): (tectonic family member 3) This gene encodes a member of the tectonic gene family which functions in Hedgehog signal transduction and development of the neural tube. Mutations in this gene have been associated with Orofaciodigital Syndrome IV and Joubert Syndrom 18. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-95663951-C-A is Benign according to our data. Variant chr10-95663951-C-A is described in ClinVar as [Benign]. Clinvar id is 1236989.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCTN3	NM_015631.6	c.*116G>T		3_prime_UTR_variant	14/14	ENST00000371217.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCTN3	ENST00000371217.10	c.*116G>T		3_prime_UTR_variant	14/14	1	NM_015631.6	P2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40549 AN: 151882 Hom.: 6225 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.301 AC: 188550 AN: 627128 Hom.: 30473 Cov.: 8 AF XY: 0.297 AC XY: 98235 AN XY: 330584

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.432

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.0474

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.267 AC: 40540 AN: 152000 Hom.: 6218 Cov.: 32 AF XY: 0.266 AC XY: 19775 AN XY: 74282

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.0421

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.246

Alfa AF: 0.323 Hom.: 3236

Bravo AF: 0.269

Asia WGS AF: 0.129 AC: 453 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.7
Dann	Benign	0.54

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: rs6946; hg19: chr10-97423708; COSMIC: COSV56446770;