11-113323597-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_017868.4(TTC12):c.222+156del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 514,116 control chromosomes in the GnomAD database, including 6,850 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1883 hom., cov: 29)
  • Exomes 𝑓: 0.16 (4967 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.983

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 -10 ACMG points.

• BP6: Variant 11-113323597-AT-A is Benign according to our data. Variant chr11-113323597-AT-A is described in ClinVar as [Benign]. Clinvar id is 1220837.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC12	NM_017868.4	c.222+156del		intron_variant		ENST00000529221.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC12	ENST00000529221.6	c.222+156del		intron_variant		2	NM_017868.4	A2

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21465 AN: 150392 Hom.: 1885 Cov.: 29

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0766

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.159 AC: 57834 AN: 363614 Hom.: 4967 AF XY: 0.161 AC XY: 29752 AN XY: 184332

Gnomad4 AFR exome AF: 0.0316

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.0822

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.143 AC: 21457 AN: 150502 Hom.: 1883 Cov.: 29 AF XY: 0.142 AC XY: 10461 AN XY: 73470

Gnomad4 AFR AF: 0.0368

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.0764

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.152

Bravo AF: 0.129

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs142060645; hg19: chr11-113194319;