10-95687616-A-T

Variant names:

• chr10-95687616-A-T
• rs10786229
• NM_015631.6:c.603T>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015631.6(TCTN3):​c.603T>A​(p.Thr201Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,613,760 control chromosomes in the GnomAD database, including 93,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10154 hom., cov: 32)
  • Exomes 𝑓: 0.33 (83540 hom.)
• Consequence: TCTN3 NM_015631.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0850

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-95687616-A-T is Benign according to our data. Variant chr10-95687616-A-T is described in ClinVar as [Benign]. Clinvar id is 130577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-95687616-A-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.085 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCTN3	NM_015631.6	c.603T>A	p.Thr201Thr	synonymous_variant	Exon 4 of 14	ENST00000371217.10	NP_056446.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCTN3	ENST00000371217.10	c.603T>A	p.Thr201Thr	synonymous_variant	Exon 4 of 14	1	NM_015631.6	ENSP00000360261.5
TCTN3	ENST00000265993.13	c.657T>A	p.Thr219Thr	synonymous_variant	Exon 4 of 14	1		ENSP00000265993.9
TCTN3	ENST00000430368.6	c.500-457T>A		intron_variant	Intron 3 of 9	2		ENSP00000387567.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53821 AN: 151956 Hom.: 10140 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.365

GnomAD3 exomes AF: 0.349 AC: 87726 AN: 251200 Hom.: 17154 AF XY: 0.352 AC XY: 47729 AN XY: 135778

Gnomad AFR exome AF: 0.409

Gnomad AMR exome AF: 0.220

Gnomad ASJ exome AF: 0.402

Gnomad EAS exome AF: 0.717

Gnomad SAS exome AF: 0.360

Gnomad FIN exome AF: 0.290

Gnomad NFE exome AF: 0.324

Gnomad OTH exome AF: 0.343

GnomAD4 exome AF: 0.331 AC: 483506 AN: 1461686 Hom.: 83540 Cov.: 38 AF XY: 0.332 AC XY: 241588 AN XY: 727136

Gnomad4 AFR exome AF: 0.408

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.408

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.354 AC: 53883 AN: 152074 Hom.: 10154 Cov.: 32 AF XY: 0.352 AC XY: 26186 AN XY: 74338

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.369

Alfa AF: 0.334 Hom.: 2810

Bravo AF: 0.357

Asia WGS AF: 0.520 AC: 1805 AN: 3478

EpiCase AF: 0.329

EpiControl AF: 0.328

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Jan 08, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Orofacial-digital syndrome IV;C3553758:Joubert syndrome 18 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.32

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: rs10786229; hg19: chr10-97447373; COSMIC: COSV105852913;