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: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• 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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4	c.59-167dupA		intron_variant	Intron 2 of 21	ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.59-186_59-185insA		intron_variant	Intron 2 of 21	2	NM_017868.4	ENSP00000433757.1

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

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;