Genetic Variant TTC12:c.-15-86C>T (chr11-113316157-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017868.4(TTC12):c.-15-86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 528,770 control chromosomes in the GnomAD database, including 22,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5269 hom., cov: 33)

Exomes 𝑓: 0.29 ( 16840 hom. )

Consequence

TTC12
NM_017868.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.03

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 11-113316157-C-T is Benign according to our data. Variant chr11-113316157-C-T is described in ClinVar as [Benign]. Clinvar id is 1253908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4 link	c.-15-86C>T		intron_variant	Intron 1 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.-15-86C>T		intron_variant	Intron 1 of 21	2	NM_017868.4	ENSP00000433757.1		Q9H892-1

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37361

AN:

151964

Hom.:

5269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.341

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.261

GnomAD4 exome

AF:

0.295

AC:

111021

AN:

376688

Hom.:

16840

Cov.:

AF XY:

0.295

AC XY:

56300

AN XY:

191078

show subpopulations

African (AFR)

AF:

0.0998

AC:

959

AN:

9612

American (AMR)

AF:

0.334

AC:

3255

AN:

9756

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

3427

AN:

10214

East Asian (EAS)

AF:

0.300

AC:

7502

AN:

25032

South Asian (SAS)

AF:

0.260

AC:

1928

AN:

7422

European-Finnish (FIN)

AF:

0.260

AC:

10013

AN:

38526

Middle Eastern (MID)

AF:

0.240

AC:

671

AN:

2796

European-Non Finnish (NFE)

AF:

0.306

AC:

77408

AN:

252984

Other (OTH)

AF:

0.288

AC:

5858

AN:

20346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3853

7706

11559

15412

19265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.246

AC:

37357

AN:

152082

Hom.:

5269

Cov.:

AF XY:

0.246

AC XY:

18284

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.106

AC:

4397

AN:

41502

American (AMR)

AF:

0.315

AC:

4817

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1214

AN:

3468

East Asian (EAS)

AF:

0.340

AC:

1755

AN:

5164

South Asian (SAS)

AF:

0.254

AC:

1227

AN:

4824

European-Finnish (FIN)

AF:

0.272

AC:

2866

AN:

10546

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.298

AC:

20239

AN:

67970

Other (OTH)

AF:

0.259

AC:

547

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1429

2858

4286

5715

7144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.262

Hom.:

896

Bravo

AF:

0.248

Asia WGS

AF:

0.299

AC:

1038

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.62

PhyloP100

1.0

PromoterAI

0.0043

Neutral

(source)

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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11-113316157-C-T

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