dbSNP rs1055076: TTC12:c.*120+524C>A (chr11-113368987-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000314756.7(TTC12):c.*120+524C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 158,828 control chromosomes in the GnomAD database, including 4,464 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4336 hom., cov: 32)

Exomes 𝑓: 0.17 ( 128 hom. )

Consequence

TTC12
ENST00000314756.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.143

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:

ENSG00000270179 (HGNC:):

ENSG00000270179 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NR_165393.1 link	n.2267C>A		non_coding_transcript_exon_variant	Exon 17 of 17
TTC12	NR_147891.2 link	n.2370+524C>A		intron_variant	Intron 22 of 22

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
TTC12	ENST00000314756.7 link	c.*120+524C>A	intron_variant	Intron 21 of 21	1	ENSP00000315160.3	Q9H892-2
TTC12	ENST00000494714.5 link	n.*120+524C>A	intron_variant	Intron 22 of 22	1	ENSP00000435291.1	Q9H892-2
ENSG00000270179	ENST00000602900.1 link	n.510C>A	non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32918

AN:

151916

Hom.:

4327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.510

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.196

GnomAD4 exome

AF:

0.170

AC:

1155

AN:

6794

Hom.:

128

Cov.:

AF XY:

0.170

AC XY:

601

AN XY:

3526

show subpopulations

African (AFR)

AF:

0.259

AC:

AN:

American (AMR)

AF:

0.198

AC:

315

AN:

1590

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

AN:

East Asian (EAS)

AF:

0.497

AC:

145

AN:

292

South Asian (SAS)

AF:

0.186

AC:

127

AN:

684

European-Finnish (FIN)

AF:

0.132

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.130

AC:

494

AN:

3786

Other (OTH)

AF:

0.152

AC:

AN:

264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

122

163

204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.217

AC:

32955

AN:

152034

Hom.:

4336

Cov.:

AF XY:

0.224

AC XY:

16618

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.311

AC:

12890

AN:

41424

American (AMR)

AF:

0.229

AC:

3503

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

521

AN:

3470

East Asian (EAS)

AF:

0.510

AC:

2628

AN:

5152

South Asian (SAS)

AF:

0.217

AC:

1043

AN:

4812

European-Finnish (FIN)

AF:

0.230

AC:

2436

AN:

10574

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.137

AC:

9311

AN:

68002

Other (OTH)

AF:

0.195

AC:

412

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1254

2508

3761

5015

6269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.164

Hom.:

6959

Bravo

AF:

0.220

Asia WGS

AF:

0.332

AC:

1153

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.33

(source)

DANN

Benign

0.36

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over