11-113323241-C-G

Position:

• chr11-113323241-C-G

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.59-47C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 1,440,014 control chromosomes in the GnomAD database, including 3,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (399 hom., cov: 32)
  • Exomes 𝑓: 0.065 (2855 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0980

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=-0.82).
• BP6: Variant 11-113323241-C-G is Benign according to our data. Variant chr11-113323241-C-G is described in ClinVar as [Benign]. Clinvar id is 1251327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC12	NM_017868.4	c.59-47C>G		intron_variant		ENST00000529221.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC12	ENST00000529221.6	c.59-47C>G		intron_variant		2	NM_017868.4	A2

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10406 AN: 151686 Hom.: 397 Cov.: 32

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0511

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.0603

GnomAD3 exomes AF: 0.0594 AC: 10398 AN: 174954 Hom.: 364 AF XY: 0.0579 AC XY: 5447 AN XY: 94048

Gnomad AFR exome AF: 0.0961

Gnomad AMR exome AF: 0.0420

Gnomad ASJ exome AF: 0.0544

Gnomad EAS exome AF: 0.0672

Gnomad SAS exome AF: 0.0523

Gnomad FIN exome AF: 0.0380

Gnomad NFE exome AF: 0.0619

Gnomad OTH exome AF: 0.0615

GnomAD4 exome AF: 0.0653 AC: 84068 AN: 1288210 Hom.: 2855 Cov.: 20 AF XY: 0.0644 AC XY: 40929 AN XY: 635940

Gnomad4 AFR exome AF: 0.0905

Gnomad4 AMR exome AF: 0.0447

Gnomad4 ASJ exome AF: 0.0581

Gnomad4 EAS exome AF: 0.0609

Gnomad4 SAS exome AF: 0.0504

Gnomad4 FIN exome AF: 0.0404

Gnomad4 NFE exome AF: 0.0674

Gnomad4 OTH exome AF: 0.0661

GnomAD4 genome AF: 0.0687 AC: 10425 AN: 151804 Hom.: 399 Cov.: 32 AF XY: 0.0674 AC XY: 5000 AN XY: 74160

Gnomad4 AFR AF: 0.0948

Gnomad4 AMR AF: 0.0510

Gnomad4 ASJ AF: 0.0571

Gnomad4 EAS AF: 0.0663

Gnomad4 SAS AF: 0.0500

Gnomad4 FIN AF: 0.0397

Gnomad4 NFE AF: 0.0641

Gnomad4 OTH AF: 0.0645

Alfa AF: 0.0615 Hom.: 63

Bravo AF: 0.0707

Asia WGS AF: 0.0820 AC: 285 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 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.68

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

LitVar

Other links and lift over

dbSNP: rs723078; hg19: chr11-113193963;