11-113316157-C-T

Position:

• chr11-113316157-C-T

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.-15-86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 528,770 control chromosomes in the GnomAD database, including 22,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5269 hom., cov: 33)
  • Exomes 𝑓: 0.29 (16840 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.03

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=-0.57).
• BP6: Variant 11-113316157-C-T is Benign according to our data. Variant chr11-113316157-C-T is described in ClinVar as [Benign]. Clinvar id is 1253908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC12	NM_017868.4	c.-15-86C>T		intron_variant		ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.-15-86C>T		intron_variant		2	NM_017868.4	ENSP00000433757	A2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37361 AN: 151964 Hom.: 5269 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.295 AC: 111021 AN: 376688 Hom.: 16840 Cov.: 6 AF XY: 0.295 AC XY: 56300 AN XY: 191078

Gnomad4 AFR exome AF: 0.0998

Gnomad4 AMR exome AF: 0.334

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.246 AC: 37357 AN: 152082 Hom.: 5269 Cov.: 33 AF XY: 0.246 AC XY: 18284 AN XY: 74340

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.259

Alfa AF: 0.262 Hom.: 896

Bravo AF: 0.248

Asia WGS AF: 0.299 AC: 1038 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	clinical testing	GeneDx	May 17, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.62

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: rs7130072; hg19: chr11-113186879; COSMIC: COSV59098253; COSMIC: COSV59098253;