11-113323102-CAAAAAAA-CAAAAAAAAAAAA

Variant names:

• chr11-113323102-C-CAAAAA
• rs34496236
• NM_017868.4:c.59-171_59-167dupAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017868.4(TTC12):​c.59-171_59-167dupAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 79,446 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 23)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.59-171_59-167dupAAAAA		intron	N/A	NP_060338.3
	TTC12	NM_001318533.2		c.59-171_59-167dupAAAAA		intron	N/A	NP_001305462.1	J3KR69
	TTC12	NM_001378063.1		c.-17-171_-17-167dupAAAAA		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_59-185insAAAAA		intron	N/A	ENSP00000433757.1	Q9H892-1
	TTC12	ENST00000314756.7	TSL:1	c.59-186_59-185insAAAAA		intron	N/A	ENSP00000315160.3	Q9H892-2
	TTC12	ENST00000494714.5	TSL:1	n.59-186_59-185insAAAAA		intron	N/A	ENSP00000435291.1	Q9H892-2

Frequencies

GnomAD3 genomes AF: 0.0000126 AC: 1 AN: 79446 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000510

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000126 AC: 1 AN: 79446 Hom.: 0 Cov.: 23 AF XY: 0.0000269 AC XY: 1 AN XY: 37148

African (AFR) AF: 0.0000510 AC: 1 AN: 19604

American (AMR) AF: 0.00 AC: 0 AN: 7022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2082

East Asian (EAS) AF: 0.00 AC: 0 AN: 2020

South Asian (SAS) AF: 0.00 AC: 0 AN: 2364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 156

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 40982

Other (OTH) AF: 0.00 AC: 0 AN: 1078

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs34496236; hg19: chr11-113193824;