11-113330009-A-G

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.504+30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00928 in 1,565,324 control chromosomes in the GnomAD database, including 857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (392 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (465 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0300

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=-0.94).
• BP6: Variant 11-113330009-A-G is Benign according to our data. Variant chr11-113330009-A-G is described in ClinVar as [Benign]. Clinvar id is 1226296.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC12	NM_017868.4	c.504+30A>G		intron_variant		ENST00000529221.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC12	ENST00000529221.6	c.504+30A>G		intron_variant		2	NM_017868.4	A2

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 6009 AN: 152118 Hom.: 385 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0430

GnomAD3 exomes AF: 0.0134 AC: 3377 AN: 251310 Hom.: 181 AF XY: 0.0122 AC XY: 1655 AN XY: 135818

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.00610

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00462

Gnomad SAS exome AF: 0.0262

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000449

Gnomad OTH exome AF: 0.00670

GnomAD4 exome AF: 0.00601 AC: 8487 AN: 1413088 Hom.: 465 Cov.: 23 AF XY: 0.00620 AC XY: 4379 AN XY: 705906

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.00739

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.00448

Gnomad4 SAS exome AF: 0.0262

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000254

Gnomad4 OTH exome AF: 0.0120

GnomAD4 genome AF: 0.0397 AC: 6038 AN: 152236 Hom.: 392 Cov.: 33 AF XY: 0.0385 AC XY: 2869 AN XY: 74434

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0219

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00424

Gnomad4 SAS AF: 0.0278

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.0425

Alfa AF: 0.0166 Hom.: 36

Bravo AF: 0.0456

Asia WGS AF: 0.0290 AC: 100 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 22, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.91
Dann	Benign	0.56

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: rs78183568; hg19: chr11-113200731;