Genetic Variant NM_017868.4:c.59-34T>C (chr11-113323254-T-C) – 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.59-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,497,306 control chromosomes in the GnomAD database, including 313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 19 hom., cov: 32)

Exomes 𝑓: 0.018 ( 294 hom. )

Consequence

TTC12
NM_017868.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.275

Publications

3 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=-0.85).

BP6

Variant 11-113323254-T-C is Benign according to our data. Variant chr11-113323254-T-C is described in ClinVar as [Benign]. Clinvar id is 1265170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4 link	c.59-34T>C		intron_variant	Intron 2 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.59-34T>C		intron_variant	Intron 2 of 21	2	NM_017868.4	ENSP00000433757.1		Q9H892-1

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1768

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00287

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0536

Gnomad FIN

AF:

0.00745

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.0163

GnomAD2 exomes

AF:

0.0163

AC:

3104

AN:

191010

AF XY:

0.0187

show subpopulations

Gnomad AFR exome

AF:

0.00225

Gnomad AMR exome

AF:

0.00761

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.000137

Gnomad FIN exome

AF:

0.00872

Gnomad NFE exome

AF:

0.0172

Gnomad OTH exome

AF:

0.0170

GnomAD4 exome

AF:

0.0176

AC:

23672

AN:

1345044

Hom.:

294

Cov.:

AF XY:

0.0184

AC XY:

12272

AN XY:

665424

show subpopulations

African (AFR)

AF:

0.00206

AC:

AN:

29554

American (AMR)

AF:

0.00844

AC:

247

AN:

29274

Ashkenazi Jewish (ASJ)

AF:

0.0100

AC:

212

AN:

21136

East Asian (EAS)

AF:

0.0000808

AC:

AN:

37108

South Asian (SAS)

AF:

0.0545

AC:

3547

AN:

65066

European-Finnish (FIN)

AF:

0.00920

AC:

452

AN:

49128

Middle Eastern (MID)

AF:

0.0246

AC:

130

AN:

5282

European-Non Finnish (NFE)

AF:

0.0172

AC:

18109

AN:

1053740

Other (OTH)

AF:

0.0166

AC:

911

AN:

54756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1091

2182

3272

4363

5454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0116

AC:

1773

AN:

152262

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

908

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00286

AC:

119

AN:

41568

American (AMR)

AF:

0.00791

AC:

121

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00836

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5170

South Asian (SAS)

AF:

0.0547

AC:

263

AN:

4812

European-Finnish (FIN)

AF:

0.00745

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0162

AC:

1100

AN:

68016

Other (OTH)

AF:

0.0161

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

178

267

356

445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.0104

Asia WGS

AF:

0.0140

AC:

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

-0.85

CADD

Benign

1.0

(source)

DANN

Benign

0.72

PhyloP100

-0.28

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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NM_017868.4:c.59-34T>C

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