dbSNP rs781810431: TTC12:p.Leu9Trp (chr11-113316283-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017868.4(TTC12):c.26T>G(p.Leu9Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000543 in 1,473,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

TTC12
NM_017868.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16600311).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC12	NM_017868.4	MANE Select	c.26T>G	p.Leu9Trp	missense	Exon 2 of 22	NP_060338.3
TTC12	NM_001318533.2		c.26T>G	p.Leu9Trp	missense	Exon 2 of 22	NP_001305462.1	J3KR69
TTC12	NM_001378064.1		c.26T>G	p.Leu9Trp	missense	Exon 2 of 22	NP_001364993.1	Q9H892-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC12	ENST00000529221.6	TSL:2 MANE Select	c.26T>G	p.Leu9Trp	missense	Exon 2 of 22	ENSP00000433757.1	Q9H892-1
TTC12	ENST00000314756.7	TSL:1	c.26T>G	p.Leu9Trp	missense	Exon 1 of 22	ENSP00000315160.3	Q9H892-2
TTC12	ENST00000494714.5	TSL:1	n.26T>G		non_coding_transcript_exon	Exon 2 of 23	ENSP00000435291.1	Q9H892-2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000112

AC:

AN:

187194

AF XY:

0.000117

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000308

Gnomad NFE exome

AF:

0.000151

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.0000507

AC:

AN:

1321710

Hom.:

Cov.:

AF XY:

0.0000598

AC XY:

AN XY:

652288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28860

American (AMR)

AF:

0.00

AC:

AN:

28252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21144

East Asian (EAS)

AF:

0.00

AC:

AN:

35916

South Asian (SAS)

AF:

0.00

AC:

AN:

57516

European-Finnish (FIN)

AF:

0.000289

AC:

AN:

48496

Middle Eastern (MID)

AF:

0.000193

AC:

AN:

5168

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

1042336

Other (OTH)

AF:

0.000111

AC:

AN:

54022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000854

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000107

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.000124

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

(source)

DANN

Benign

0.96

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.19

M_CAP

Benign

0.021

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.75

PhyloP100

3.9

PROVEAN

Benign

0.39

REVEL

Benign

0.14

Sift

Pathogenic

0.0

MVP

0.52

ClinPred

0.31

GERP RS

4.9

PromoterAI

-0.0082

Neutral

(source)

Varity_R

0.10

Mutation Taster

=83/17

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over