11-113323102-C-CA

Variant names:

• chr11-113323102-C-CA
• rs34496236
• NM_017868.4:c.59-167dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_017868.4(TTC12):​c.59-167dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 79,196 control chromosomes in the GnomAD database, including 1,861 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (1861 hom., cov: 23)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

Genes affected

TTC12 (HGNC:23700): (tetratricopeptide repeat domain 12) Involved in axonemal dynein complex assembly and sperm axoneme assembly. Located in centrosome and cytoplasm. Implicated in primary ciliary dyskinesia 45. [provided by Alliance of Genome Resources, Apr 2022]

TTC12 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 45

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-113323102-C-CA is Benign according to our data. Variant chr11-113323102-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1270524.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017868.4. 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
	TTC12	NM_017868.4	MANE Select	c.59-167dupA		intron	N/A	NP_060338.3
	TTC12	NM_001318533.2		c.59-167dupA		intron	N/A	NP_001305462.1	J3KR69
	TTC12	NM_001378063.1		c.-17-167dupA		intron	N/A	NP_001364992.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC12	ENST00000529221.6	TSL:2 MANE Select	c.59-186_59-185insA		intron	N/A	ENSP00000433757.1	Q9H892-1
	TTC12	ENST00000314756.7	TSL:1	c.59-186_59-185insA		intron	N/A	ENSP00000315160.3	Q9H892-2
	TTC12	ENST00000494714.5	TSL:1	n.59-186_59-185insA		intron	N/A	ENSP00000435291.1	Q9H892-2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 21266 AN: 79190 Hom.: 1864 Cov.: 23

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.268 AC: 21253 AN: 79196 Hom.: 1861 Cov.: 23 AF XY: 0.266 AC XY: 9857 AN XY: 37054

African (AFR) AF: 0.228 AC: 4469 AN: 19608

American (AMR) AF: 0.251 AC: 1763 AN: 7018

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 567 AN: 2066

East Asian (EAS) AF: 0.167 AC: 336 AN: 2010

South Asian (SAS) AF: 0.371 AC: 866 AN: 2334

European-Finnish (FIN) AF: 0.219 AC: 768 AN: 3514

Middle Eastern (MID) AF: 0.352 AC: 50 AN: 142

European-Non Finnish (NFE) AF: 0.292 AC: 11905 AN: 40810

Other (OTH) AF: 0.275 AC: 296 AN: 1078

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34496236; hg19: chr11-113193824;