rs10882649

Variant names:

• chr10-95666329-A-G
• rs10882649
• NM_015631.6:c.1591-2029T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-95666329-A-G
• chr10-95666329-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015631.6(TCTN3):​c.1591-2029T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,462 control chromosomes in the GnomAD database, including 6,227 homozygotes. 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: 𝑓 0.27 (6227 hom., cov: 29)
• Consequence: TCTN3 NM_015631.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 10 publications found

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]

TCTN3 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• orofaciodigital syndrome IV

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine
• Joubert syndrome 18

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015631.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN3	NM_015631.6	MANE Select	c.1591-2029T>C		intron	N/A	NP_056446.4
	TCTN3	NM_001410982.1		c.1495-2029T>C		intron	N/A	NP_001397911.1
	TCTN3	NM_001143973.2		c.1147-2029T>C		intron	N/A	NP_001137445.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN3	ENST00000371217.10	TSL:1 MANE Select	c.1591-2029T>C		intron	N/A	ENSP00000360261.5
	TCTN3	ENST00000265993.13	TSL:1	c.1645-2029T>C		intron	N/A	ENSP00000265993.9
	TCTN3	ENST00000614499.5	TSL:1	c.1630-2029T>C		intron	N/A	ENSP00000483364.2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40469 AN: 151346 Hom.: 6234 Cov.: 29

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0427

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.249

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.267 AC: 40460 AN: 151462 Hom.: 6227 Cov.: 29 AF XY: 0.267 AC XY: 19726 AN XY: 73976

African (AFR) AF: 0.137 AC: 5651 AN: 41224

American (AMR) AF: 0.382 AC: 5810 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3468

East Asian (EAS) AF: 0.0422 AC: 218 AN: 5162

South Asian (SAS) AF: 0.219 AC: 1050 AN: 4804

European-Finnish (FIN) AF: 0.310 AC: 3237 AN: 10426

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22827 AN: 67854

Other (OTH) AF: 0.246 AC: 518 AN: 2104

Alfa AF: 0.315 Hom.: 10574

Bravo AF: 0.269

Asia WGS AF: 0.129 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.6
DANN	Benign	0.76
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10882649; hg19: chr10-97426086;