Genetic Variant TTC12:c.59-167delA (chr11-113323102-CA-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_017868.4(TTC12):c.59-167delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 79,444 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 10 hom., cov: 23)

Consequence

TTC12
NM_017868.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.19

Publications

0 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: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
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 11-113323102-CA-C is Benign according to our data. Variant chr11-113323102-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1225031.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0185 (1470/79444) while in subpopulation AFR AF = 0.0401 (787/19632). AF 95% confidence interval is 0.0378. There are 10 homozygotes in GnomAd4. There are 732 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017868.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTC12	NM_017868.4	MANE Select	c.59-167delA	intron	N/A	NP_060338.3
TTC12	NM_001318533.2		c.59-167delA	intron	N/A	NP_001305462.1	J3KR69
TTC12	NM_001378063.1		c.-17-167delA	intron	N/A	NP_001364992.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTC12	ENST00000529221.6	TSL:2 MANE Select	c.59-185delA	intron	N/A	ENSP00000433757.1	Q9H892-1
TTC12	ENST00000314756.7	TSL:1	c.59-185delA	intron	N/A	ENSP00000315160.3	Q9H892-2
TTC12	ENST00000494714.5	TSL:1	n.59-185delA	intron	N/A	ENSP00000435291.1	Q9H892-2

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

1464

AN:

79438

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0399

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0257

Gnomad SAS

AF:

0.0254

Gnomad FIN

AF:

0.0227

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.00959

Gnomad OTH

AF:

0.00928

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0185

AC:

1470

AN:

79444

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

732

AN XY:

37154

show subpopulations

African (AFR)

AF:

0.0401

AC:

787

AN:

19632

American (AMR)

AF:

0.0118

AC:

AN:

7030

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

2082

East Asian (EAS)

AF:

0.0258

AC:

AN:

2014

South Asian (SAS)

AF:

0.0256

AC:

AN:

2344

European-Finnish (FIN)

AF:

0.0227

AC:

AN:

3522

Middle Eastern (MID)

AF:

0.00694

AC:

AN:

144

European-Non Finnish (NFE)

AF:

0.00959

AC:

393

AN:

40978

Other (OTH)

AF:

0.0102

AC:

AN:

1082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

110

165

220

275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over