rs719804

Positions:

• chr11-113364053-A-G

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.1816+126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 633,980 control chromosomes in the GnomAD database, including 16,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3665 hom., cov: 33)
  • Exomes 𝑓: 0.23 (12911 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.724

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=-0.92).
• BP6: Variant 11-113364053-A-G is Benign according to our data. Variant chr11-113364053-A-G is described in ClinVar as [Benign]. Clinvar id is 1275576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC12	NM_017868.4	c.1816+126A>G		intron_variant		ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.1816+126A>G		intron_variant		2	NM_017868.4	ENSP00000433757	A2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32890 AN: 152152 Hom.: 3665 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.225 AC: 108512 AN: 481710 Hom.: 12911 AF XY: 0.228 AC XY: 58140 AN XY: 254720

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.247

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.216 AC: 32923 AN: 152270 Hom.: 3665 Cov.: 33 AF XY: 0.212 AC XY: 15782 AN XY: 74470

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.213

Alfa AF: 0.234 Hom.: 5564

Bravo AF: 0.213

Asia WGS AF: 0.180 AC: 628 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	-0.92
CADD	Benign	0.74
DANN	Benign	0.64

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: rs719804; hg19: chr11-113234775;