11-113323597-ATTT-ATTTTT

Variant names:

• chr11-113323597-A-ATT
• rs142060645
• NM_017868.4:c.222+155_222+156dupTT

Variant summary

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

The NM_017868.4(TTC12):​c.222+155_222+156dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 364,898 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4	c.222+155_222+156dupTT		intron_variant	Intron 3 of 21	ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.222+146_222+147insTT		intron_variant	Intron 3 of 21	2	NM_017868.4	ENSP00000433757.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000548 AC: 2 AN: 364898 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 185010

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000107 AC: 1 AN: 9314

American (AMR) AF: 0.00 AC: 0 AN: 9820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10008

East Asian (EAS) AF: 0.00 AC: 0 AN: 23662

South Asian (SAS) AF: 0.00 AC: 0 AN: 12356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1506

European-Non Finnish (NFE) AF: 0.00000392 AC: 1 AN: 254848

Other (OTH) AF: 0.00 AC: 0 AN: 20604

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.98

Splicing

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

Other links and lift over

dbSNP: rs142060645; hg19: chr11-113194319;