rs10882649

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCTN3	NM_015631.6	c.1591-2029T>C		intron_variant		ENST00000371217.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCTN3	ENST00000371217.10	c.1591-2029T>C		intron_variant		1	NM_015631.6	P2

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

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0422

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.246

Alfa AF: 0.321 Hom.: 8400

Bravo AF: 0.269

Asia WGS AF: 0.129 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.6
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs10882649; hg19: chr10-97426086;