11-113323254-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017868.4(TTC12):c.59-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,497,306 control chromosomes in the GnomAD database, including 313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (19 hom., cov: 32)
  • Exomes 𝑓: 0.018 (294 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.275

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-113323254-T-C is Benign according to our data. Variant chr11-113323254-T-C is described in ClinVar as [Benign]. Clinvar id is 1265170.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC12	NM_017868.4	c.59-34T>C		intron_variant		ENST00000529221.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC12	ENST00000529221.6	c.59-34T>C		intron_variant		2	NM_017868.4	A2

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1768 AN: 152144 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00287

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.00745

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.0163 AC: 3104 AN: 191010 Hom.: 45 AF XY: 0.0187 AC XY: 1933 AN XY: 103354

Gnomad AFR exome AF: 0.00225

Gnomad AMR exome AF: 0.00761

Gnomad ASJ exome AF: 0.0108

Gnomad EAS exome AF: 0.000137

Gnomad SAS exome AF: 0.0535

Gnomad FIN exome AF: 0.00872

Gnomad NFE exome AF: 0.0172

Gnomad OTH exome AF: 0.0170

GnomAD4 exome AF: 0.0176 AC: 23672 AN: 1345044 Hom.: 294 Cov.: 26 AF XY: 0.0184 AC XY: 12272 AN XY: 665424

Gnomad4 AFR exome AF: 0.00206

Gnomad4 AMR exome AF: 0.00844

Gnomad4 ASJ exome AF: 0.0100

Gnomad4 EAS exome AF: 0.0000808

Gnomad4 SAS exome AF: 0.0545

Gnomad4 FIN exome AF: 0.00920

Gnomad4 NFE exome AF: 0.0172

Gnomad4 OTH exome AF: 0.0166

GnomAD4 genome AF: 0.0116 AC: 1773 AN: 152262 Hom.: 19 Cov.: 32 AF XY: 0.0122 AC XY: 908 AN XY: 74434

Gnomad4 AFR AF: 0.00286

Gnomad4 AMR AF: 0.00791

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0547

Gnomad4 FIN AF: 0.00745

Gnomad4 NFE AF: 0.0162

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0124 Hom.: 5

Bravo AF: 0.0104

Asia WGS AF: 0.0140 AC: 50 AN: 3478

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.0
Dann	Benign	0.72

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: rs45457596; hg19: chr11-113193976;