11-113329987-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.504+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,605,108 control chromosomes in the GnomAD database, including 317,243 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30800 hom., cov: 32)
  • Exomes 𝑓: 0.63 (286443 hom.)
• Consequence: TTC12 NM_017868.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003587
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.506

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=-0.81).
• BP6: Variant 11-113329987-G-A is Benign according to our data. Variant chr11-113329987-G-A is described in ClinVar as [Benign]. Clinvar id is 1287032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC12	NM_017868.4	c.504+8G>A		splice_region_variant, intron_variant		ENST00000529221.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC12	ENST00000529221.6	c.504+8G>A		splice_region_variant, intron_variant		2	NM_017868.4	A2

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96352 AN: 151940 Hom.: 30786 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.643

GnomAD3 exomes AF: 0.605 AC: 152147 AN: 251344 Hom.: 46941 AF XY: 0.611 AC XY: 82955 AN XY: 135848

Gnomad AFR exome AF: 0.679

Gnomad AMR exome AF: 0.452

Gnomad ASJ exome AF: 0.657

Gnomad EAS exome AF: 0.529

Gnomad SAS exome AF: 0.597

Gnomad FIN exome AF: 0.685

Gnomad NFE exome AF: 0.635

Gnomad OTH exome AF: 0.624

GnomAD4 exome AF: 0.626 AC: 908914 AN: 1453048 Hom.: 286443 Cov.: 30 AF XY: 0.626 AC XY: 452668 AN XY: 723382

Gnomad4 AFR exome AF: 0.681

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.666

Gnomad4 EAS exome AF: 0.570

Gnomad4 SAS exome AF: 0.604

Gnomad4 FIN exome AF: 0.684

Gnomad4 NFE exome AF: 0.630

Gnomad4 OTH exome AF: 0.633

GnomAD4 genome AF: 0.634 AC: 96414 AN: 152060 Hom.: 30800 Cov.: 32 AF XY: 0.633 AC XY: 47051 AN XY: 74318

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.639

Alfa AF: 0.631 Hom.: 40718

Bravo AF: 0.624

Asia WGS AF: 0.544 AC: 1893 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ciliary dyskinesia, primary, 45 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided Benign:1

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	-0.81
Cadd	Benign	3.8
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000036
dbscSNV1_RF	Benign	0.0
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: rs2303380; hg19: chr11-113200709; COSMIC: COSV59099317; COSMIC: COSV59099317;