chr11-113316054-G-A

Position:

• chr11-113316054-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017868.4(TTC12):​c.-15-189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 385,256 control chromosomes in the GnomAD database, including 101,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40742 hom., cov: 33)
  • Exomes 𝑓: 0.72 (60699 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Scores: Splicing: ADA: 0.00002892
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.775

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-113316054-G-A is Benign according to our data. Variant chr11-113316054-G-A is described in ClinVar as [Benign]. Clinvar id is 1250214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC12	NM_017868.4	c.-15-189G>A		intron_variant		ENST00000529221.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC12	ENST00000529221.6	c.-15-189G>A		intron_variant		2	NM_017868.4	A2

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110808 AN: 152044 Hom.: 40718 Cov.: 33

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.723

GnomAD4 exome AF: 0.715 AC: 166770 AN: 233094 Hom.: 60699 Cov.: 3 AF XY: 0.717 AC XY: 84862 AN XY: 118382

Gnomad4 AFR exome AF: 0.742

Gnomad4 AMR exome AF: 0.647

Gnomad4 ASJ exome AF: 0.765

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.782

Gnomad4 FIN exome AF: 0.725

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.719

GnomAD4 genome AF: 0.729 AC: 110881 AN: 152162 Hom.: 40742 Cov.: 33 AF XY: 0.725 AC XY: 53954 AN XY: 74372

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.724

Alfa AF: 0.743 Hom.: 46750

Bravo AF: 0.723

Asia WGS AF: 0.681 AC: 2368 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.88
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000029
dbscSNV1_RF	Benign	0.044
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

LitVar

Other links and lift over

dbSNP: rs2236709; hg19: chr11-113186776;