Genetic Variant NM_017868.4:c.-15-189G>A (chr11-113316054-G-A) – 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.-15-189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 385,256 control chromosomes in the GnomAD database, including 101,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 40742 hom., cov: 33)

Exomes 𝑓: 0.72 ( 60699 hom. )

Consequence

TTC12
NM_017868.4 intron

Scores

Splicing: ADA: 0.00002892

Clinical Significance

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

Conservation

PhyloP100: -0.775

Publications

22 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=-0.86).

BP6

Variant 11-113316054-G-A is Benign according to our data. Variant chr11-113316054-G-A is described in ClinVar as [Benign]. Clinvar id is 1250214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4 link	c.-15-189G>A		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.-15-189G>A		intron_variant	Intron 1 of 21	2	NM_017868.4	ENSP00000433757.1		Q9H892-1

Frequencies

GnomAD3 genomes

AF:

0.729

AC:

110808

AN:

152044

Hom.:

40718

Cov.:

show subpopulations

Gnomad AFR

AF:

0.748

Gnomad AMI

AF:

0.706

Gnomad AMR

AF:

0.657

Gnomad ASJ

AF:

0.752

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.767

Gnomad FIN

AF:

0.729

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.748

Gnomad OTH

AF:

0.723

GnomAD4 exome

AF:

0.715

AC:

166770

AN:

233094

Hom.:

60699

Cov.:

AF XY:

0.717

AC XY:

84862

AN XY:

118382

show subpopulations

African (AFR)

AF:

0.742

AC:

5039

AN:

6792

American (AMR)

AF:

0.647

AC:

4475

AN:

6916

Ashkenazi Jewish (ASJ)

AF:

0.765

AC:

6629

AN:

8666

East Asian (EAS)

AF:

0.450

AC:

9572

AN:

21276

South Asian (SAS)

AF:

0.782

AC:

1632

AN:

2088

European-Finnish (FIN)

AF:

0.725

AC:

17104

AN:

23606

Middle Eastern (MID)

AF:

0.717

AC:

881

AN:

1228

European-Non Finnish (NFE)

AF:

0.750

AC:

110497

AN:

147298

Other (OTH)

AF:

0.719

AC:

10941

AN:

15224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2098

4197

6295

8394

10492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.729

AC:

110881

AN:

152162

Hom.:

40742

Cov.:

AF XY:

0.725

AC XY:

53954

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.748

AC:

31053

AN:

41516

American (AMR)

AF:

0.656

AC:

10029

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.752

AC:

2611

AN:

3470

East Asian (EAS)

AF:

0.490

AC:

2534

AN:

5170

South Asian (SAS)

AF:

0.767

AC:

3700

AN:

4824

European-Finnish (FIN)

AF:

0.729

AC:

7706

AN:

10568

Middle Eastern (MID)

AF:

0.718

AC:

211

AN:

294

European-Non Finnish (NFE)

AF:

0.748

AC:

50866

AN:

68012

Other (OTH)

AF:

0.724

AC:

1530

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1548

3096

4645

6193

7741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.741

Hom.:

61615

Bravo

AF:

0.723

Asia WGS

AF:

0.681

AC:

2368

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 15, 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

-0.86

CADD

Benign

0.88

(source)

DANN

Benign

0.38

PhyloP100

-0.78

PromoterAI

-0.035

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000029

dbscSNV1_RF

Benign

0.044

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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NM_017868.4:c.-15-189G>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