11-113323102-CAAAAAAA-CAAAAA

Variant names:

• chr11-113323102-CAA-C
• rs34496236
• NM_017868.4:c.59-168_59-167delAA

Variant summary

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

The NM_017868.4(TTC12):​c.59-168_59-167delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000353 in 79,412 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 0.00035 (0 hom., cov: 23)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• 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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4	c.59-168_59-167delAA		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.59-185_59-184delAA		intron_variant	Intron 2 of 21	2	NM_017868.4	ENSP00000433757.1

Frequencies

GnomAD3 genomes AF: 0.000353 AC: 28 AN: 79406 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000570

Gnomad ASJ AF: 0.000481

Gnomad EAS AF: 0.000496

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000569

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000244

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000353 AC: 28 AN: 79412 Hom.: 0 Cov.: 23 AF XY: 0.000377 AC XY: 14 AN XY: 37138

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

African (AFR) AF: 0.000458 AC: 9 AN: 19634

American (AMR) AF: 0.000569 AC: 4 AN: 7028

Ashkenazi Jewish (ASJ) AF: 0.000481 AC: 1 AN: 2080

East Asian (EAS) AF: 0.000497 AC: 1 AN: 2012

South Asian (SAS) AF: 0.00 AC: 0 AN: 2344

European-Finnish (FIN) AF: 0.000569 AC: 2 AN: 3514

Middle Eastern (MID) AF: 0.00694 AC: 1 AN: 144

European-Non Finnish (NFE) AF: 0.000244 AC: 10 AN: 40958

Other (OTH) AF: 0.00 AC: 0 AN: 1082

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000073), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism

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;