11-113338706-C-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.577-68C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,256,456 control chromosomes in the GnomAD database, including 125,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (11128 hom., cov: 32)
  • Exomes 𝑓: 0.44 (114588 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.422

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=-0.83).
• BP6: Variant 11-113338706-C-G is Benign according to our data. Variant chr11-113338706-C-G is described in ClinVar as [Benign]. Clinvar id is 1277251.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC12	NM_017868.4	c.577-68C>G		intron_variant		ENST00000529221.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC12	ENST00000529221.6	c.577-68C>G		intron_variant		2	NM_017868.4	A2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52240 AN: 151962 Hom.: 11139 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.0523

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.385

GnomAD4 exome AF: 0.440 AC: 486295 AN: 1104378 Hom.: 114588 AF XY: 0.441 AC XY: 248480 AN XY: 563930

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.0534

Gnomad4 SAS exome AF: 0.355

Gnomad4 FIN exome AF: 0.463

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.343 AC: 52222 AN: 152078 Hom.: 11128 Cov.: 32 AF XY: 0.340 AC XY: 25251 AN XY: 74328

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.0519

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.384

Alfa AF: 0.417 Hom.: 1864

Bravo AF: 0.321

Asia WGS AF: 0.178 AC: 618 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 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.66
Dann	Benign	0.39

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: rs10891536; hg19: chr11-113209428; COSMIC: COSV59098510; COSMIC: COSV59098510;