11-113363957-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017868.4(TTC12):​c.1816+30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,509,252 control chromosomes in the GnomAD database, including 269,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23090 hom., cov: 34)
Exomes 𝑓: 0.60 ( 246782 hom. )

Consequence

TTC12
NM_017868.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.15
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 11-113363957-T-C is Benign according to our data. Variant chr11-113363957-T-C is described in ClinVar as [Benign]. Clinvar id is 1280036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TTC12NM_017868.4 linkuse as main transcriptc.1816+30T>C intron_variant ENST00000529221.6 NP_060338.3 Q9H892-1A8K8G6Q53G14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TTC12ENST00000529221.6 linkuse as main transcriptc.1816+30T>C intron_variant 2 NM_017868.4 ENSP00000433757.1 Q9H892-1

Frequencies

GnomAD3 genomes
AF:
0.541
AC:
82283
AN:
152096
Hom.:
23083
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.401
Gnomad AMI
AF:
0.673
Gnomad AMR
AF:
0.487
Gnomad ASJ
AF:
0.618
Gnomad EAS
AF:
0.529
Gnomad SAS
AF:
0.515
Gnomad FIN
AF:
0.654
Gnomad MID
AF:
0.570
Gnomad NFE
AF:
0.617
Gnomad OTH
AF:
0.574
GnomAD3 exomes
AF:
0.565
AC:
136094
AN:
240964
Hom.:
39409
AF XY:
0.574
AC XY:
74710
AN XY:
130084
show subpopulations
Gnomad AFR exome
AF:
0.395
Gnomad AMR exome
AF:
0.424
Gnomad ASJ exome
AF:
0.629
Gnomad EAS exome
AF:
0.525
Gnomad SAS exome
AF:
0.532
Gnomad FIN exome
AF:
0.658
Gnomad NFE exome
AF:
0.623
Gnomad OTH exome
AF:
0.593
GnomAD4 exome
AF:
0.600
AC:
813611
AN:
1357038
Hom.:
246782
Cov.:
19
AF XY:
0.600
AC XY:
408048
AN XY:
680288
show subpopulations
Gnomad4 AFR exome
AF:
0.392
Gnomad4 AMR exome
AF:
0.439
Gnomad4 ASJ exome
AF:
0.633
Gnomad4 EAS exome
AF:
0.545
Gnomad4 SAS exome
AF:
0.536
Gnomad4 FIN exome
AF:
0.658
Gnomad4 NFE exome
AF:
0.617
Gnomad4 OTH exome
AF:
0.593
GnomAD4 genome
AF:
0.541
AC:
82324
AN:
152214
Hom.:
23090
Cov.:
34
AF XY:
0.541
AC XY:
40270
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.402
Gnomad4 AMR
AF:
0.486
Gnomad4 ASJ
AF:
0.618
Gnomad4 EAS
AF:
0.529
Gnomad4 SAS
AF:
0.515
Gnomad4 FIN
AF:
0.654
Gnomad4 NFE
AF:
0.617
Gnomad4 OTH
AF:
0.570
Alfa
AF:
0.603
Hom.:
60795
Bravo
AF:
0.524
Asia WGS
AF:
0.456
AC:
1586
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 15, 2021- -
Ciliary dyskinesia, primary, 45 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.47
DANN
Benign
0.28
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs719802; hg19: chr11-113234679; COSMIC: COSV59099686; COSMIC: COSV59099686; API