11-113323102-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_017868.4(TTC12):c.59-167del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 79,444 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.019 (10 hom., cov: 23)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.19

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 -10 ACMG points.

• BP6: Variant 11-113323102-CA-C is Benign according to our data. Variant chr11-113323102-CA-C is described in ClinVar as [Benign]. Clinvar id is 1225031.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0185 (1470/79444) while in subpopulation AFR AF= 0.0401 (787/19632). AF 95% confidence interval is 0.0378. There are 10 homozygotes in gnomad4. There are 732 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC12	NM_017868.4	c.59-167del		intron_variant		ENST00000529221.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC12	ENST00000529221.6	c.59-167del		intron_variant		2	NM_017868.4	A2

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 1464 AN: 79438 Hom.: 10 Cov.: 23

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0257

Gnomad SAS AF: 0.0254

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.00959

Gnomad OTH AF: 0.00928

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0185 AC: 1470 AN: 79444 Hom.: 10 Cov.: 23 AF XY: 0.0197 AC XY: 732 AN XY: 37154

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0258

Gnomad4 SAS AF: 0.0256

Gnomad4 FIN AF: 0.0227

Gnomad4 NFE AF: 0.00959

Gnomad4 OTH AF: 0.0102

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 19, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs34496236; hg19: chr11-113193824;