10-95664022-A-G

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.*45T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,564,550 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (61 hom.)
• Consequence: TCTN3 NM_015631.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.886

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=-0.83).
• BP6: Variant 10-95664022-A-G is Benign according to our data. Variant chr10-95664022-A-G is described in ClinVar as [Benign]. Clinvar id is 1236793.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCTN3	NM_015631.6	c.*45T>C		3_prime_UTR_variant	14/14	ENST00000371217.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCTN3	ENST00000371217.10	c.*45T>C		3_prime_UTR_variant	14/14	1	NM_015631.6	P2

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2392 AN: 152168 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00403 AC: 1000 AN: 247848 Hom.: 28 AF XY: 0.00306 AC XY: 410 AN XY: 134174

Gnomad AFR exome AF: 0.0563

Gnomad AMR exome AF: 0.00219

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000133

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.00166

GnomAD4 exome AF: 0.00172 AC: 2427 AN: 1412264 Hom.: 61 Cov.: 26 AF XY: 0.00153 AC XY: 1081 AN XY: 704788

Gnomad4 AFR exome AF: 0.0600

Gnomad4 AMR exome AF: 0.00237

Gnomad4 ASJ exome AF: 0.0000782

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000319

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000795

Gnomad4 OTH exome AF: 0.00407

GnomAD4 genome AF: 0.0157 AC: 2397 AN: 152286 Hom.: 60 Cov.: 32 AF XY: 0.0153 AC XY: 1137 AN XY: 74462

Gnomad4 AFR AF: 0.0548

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.00869 Hom.: 6

Bravo AF: 0.0183

Asia WGS AF: 0.00549 AC: 19 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

Sep 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.8
Dann	Benign	0.63

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: rs74150980; hg19: chr10-97423779;