rs11188434

Variant names:

• chr10-95687730-T-A
• rs11188434
• NM_015631.6:c.500-11A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-95687730-T-A
• chr10-95687730-T-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_015631.6(TCTN3):​c.500-11A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,597,844 control chromosomes in the GnomAD database, including 20,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2983 hom., cov: 33)
  • Exomes 𝑓: 0.15 (17558 hom.)
• Consequence: TCTN3 NM_015631.6 intron
• Scores: Splicing: ADA: 0.5724
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.552
• Publications: 6 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia
• Joubert syndrome 18

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 10-95687730-T-A is Benign according to our data. Variant chr10-95687730-T-A is described in ClinVar as Benign. ClinVar VariationId is 260669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN3	NM_015631.6	MANE Select	c.500-11A>T		intron	N/A	NP_056446.4	Q6NUS6-1
	TCTN3	NM_001410982.1		c.500-11A>T		intron	N/A	NP_001397911.1	A0A7P0TB57
	TCTN3	NM_001143973.2		c.500-571A>T		intron	N/A	NP_001137445.1	Q6NUS6-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN3	ENST00000371217.10	TSL:1 MANE Select	c.500-11A>T		intron	N/A	ENSP00000360261.5	Q6NUS6-1
	TCTN3	ENST00000265993.13	TSL:1	c.554-11A>T		intron	N/A	ENSP00000265993.9	A0A0C4DFN5
	TCTN3	ENST00000614499.5	TSL:1	c.554-11A>T		intron	N/A	ENSP00000483364.2	A0A804G9W2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28219 AN: 152152 Hom.: 2984 Cov.: 33

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.216

GnomAD2 exomes AF: 0.159 AC: 36990 AN: 231936 AF XY: 0.162

Gnomad AFR exome AF: 0.279

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.286

Gnomad EAS exome AF: 0.142

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.149 AC: 215691 AN: 1445574 Hom.: 17558 Cov.: 32 AF XY: 0.151 AC XY: 108849 AN XY: 718524

African (AFR) AF: 0.281 AC: 9092 AN: 32348

American (AMR) AF: 0.107 AC: 4237 AN: 39778

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 7174 AN: 25372

East Asian (EAS) AF: 0.128 AC: 5088 AN: 39620

South Asian (SAS) AF: 0.194 AC: 15954 AN: 82072

European-Finnish (FIN) AF: 0.0971 AC: 5173 AN: 53264

Middle Eastern (MID) AF: 0.285 AC: 1625 AN: 5698

European-Non Finnish (NFE) AF: 0.142 AC: 157132 AN: 1107710

Other (OTH) AF: 0.171 AC: 10216 AN: 59712

GnomAD4 genome AF: 0.185 AC: 28233 AN: 152270 Hom.: 2983 Cov.: 33 AF XY: 0.183 AC XY: 13644 AN XY: 74448

African (AFR) AF: 0.276 AC: 11467 AN: 41534

American (AMR) AF: 0.144 AC: 2201 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 976 AN: 3470

East Asian (EAS) AF: 0.135 AC: 700 AN: 5190

South Asian (SAS) AF: 0.198 AC: 954 AN: 4828

European-Finnish (FIN) AF: 0.105 AC: 1118 AN: 10616

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10142 AN: 68018

Other (OTH) AF: 0.215 AC: 455 AN: 2116

Alfa AF: 0.180 Hom.: 513

Bravo AF: 0.191

Asia WGS AF: 0.165 AC: 576 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)
-	-	1	Orofacial-digital syndrome IV;C3553758:Joubert syndrome 18 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Benign	0.86
PhyloP100		0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.57
dbscSNV1_RF	Benign	0.62
SpliceAI score (max)		0.060		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: rs11188434; hg19: chr10-97447487;