Genetic Variant TTC12:c.222+156delT (chr11-113323597-AT-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_017868.4(TTC12):c.222+156delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 514,116 control chromosomes in the GnomAD database, including 6,850 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1883 hom., cov: 29)

Exomes 𝑓: 0.16 ( 4967 hom. )

Consequence

TTC12
NM_017868.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.983

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 11-113323597-AT-A is Benign according to our data. Variant chr11-113323597-AT-A is described in ClinVar as [Benign]. Clinvar id is 1220837.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4 link	c.222+156delT		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+147delT		intron_variant	Intron 3 of 21	2	NM_017868.4	ENSP00000433757.1		Q9H892-1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21465

AN:

150392

Hom.:

1885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0369

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.0766

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.150

GnomAD4 exome

AF:

0.159

AC:

57834

AN:

363614

Hom.:

4967

AF XY:

0.161

AC XY:

29752

AN XY:

184332

show subpopulations

African (AFR)

AF:

0.0316

AC:

293

AN:

9282

American (AMR)

AF:

0.121

AC:

1186

AN:

9770

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

1897

AN:

9984

East Asian (EAS)

AF:

0.0822

AC:

1938

AN:

23582

South Asian (SAS)

AF:

0.202

AC:

2475

AN:

12266

European-Finnish (FIN)

AF:

0.176

AC:

3992

AN:

22696

Middle Eastern (MID)

AF:

0.183

AC:

275

AN:

1506

European-Non Finnish (NFE)

AF:

0.168

AC:

42602

AN:

253986

Other (OTH)

AF:

0.155

AC:

3176

AN:

20542

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2286

4572

6859

9145

11431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.143

AC:

21457

AN:

150502

Hom.:

1883

Cov.:

AF XY:

0.142

AC XY:

10461

AN XY:

73470

show subpopulations

African (AFR)

AF:

0.0368

AC:

1508

AN:

40934

American (AMR)

AF:

0.122

AC:

1843

AN:

15100

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

627

AN:

3458

East Asian (EAS)

AF:

0.0764

AC:

392

AN:

5132

South Asian (SAS)

AF:

0.223

AC:

1059

AN:

4744

European-Finnish (FIN)

AF:

0.176

AC:

1821

AN:

10330

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13573

AN:

67504

Other (OTH)

AF:

0.152

AC:

319

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

919

1839

2758

3678

4597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0963

Hom.:

165

Bravo

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 17, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.98

Mutation Taster

=100/0

polymorphism (auto)

(source)

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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11-113323597-AT-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over