Genetic Variant NM_017868.4:c.222+154_222+156delTTT (chr11-113323597-ATTT-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_017868.4(TTC12):c.222+154_222+156delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 364,938 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: 0.0000027 ( 0 hom. )

Consequence

TTC12
NM_017868.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.171

Publications

1 publications found

Variant links:

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

TTC12 links:

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ACMG classification

Classification was made for transcript

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 link	c.222+154_222+156delTTT		intron_variant	Intron 3 of 21	ENST00000529221.6	NP_060338.3	Q9H892-1A8K8G6Q53G14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6 link	c.222+147_222+149delTTT		intron_variant	Intron 3 of 21	2	NM_017868.4	ENSP00000433757.1		Q9H892-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

364938

Hom.:

AF XY:

0.00000540

AC XY:

AN XY:

185030

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9314

American (AMR)

AF:

0.00

AC:

AN:

9820

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10012

East Asian (EAS)

AF:

0.00

AC:

AN:

23670

South Asian (SAS)

AF:

0.00

AC:

AN:

12356

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1506

European-Non Finnish (NFE)

AF:

0.00000392

AC:

AN:

254874

Other (OTH)

AF:

0.00

AC:

AN:

20606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

165

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.17

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over