11-113329836-A-G

Position:

• chr11-113329836-A-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.445-84A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,125,682 control chromosomes in the GnomAD database, including 21,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3505 hom., cov: 33)
  • Exomes 𝑓: 0.18 (18330 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.36

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=-0.95).
• BP6: Variant 11-113329836-A-G is Benign according to our data. Variant chr11-113329836-A-G is described in ClinVar as [Benign]. Clinvar id is 1250786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC12	NM_017868.4	c.445-84A>G		intron_variant		ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.445-84A>G		intron_variant		2	NM_017868.4	ENSP00000433757	A2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30578 AN: 152022 Hom.: 3497 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.175 AC: 170452 AN: 973542 Hom.: 18330 Cov.: 13 AF XY: 0.176 AC XY: 88872 AN XY: 505690

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.515

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.201 AC: 30607 AN: 152140 Hom.: 3505 Cov.: 33 AF XY: 0.207 AC XY: 15390 AN XY: 74386

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.183

Alfa AF: 0.172 Hom.: 407

Bravo AF: 0.202

Asia WGS AF: 0.329 AC: 1141 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 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.13
DANN	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7928978; hg19: chr11-113200558;