11-113323102-CAAAAAAA-CAAAAAA

Variant names:

• chr11-113323102-CA-C
• rs34496236
• NM_017868.4:c.59-167delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_017868.4(TTC12):​c.59-167delA 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
• Publications: 0 publications found

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]

TTC12 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 45

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4	c.59-167delA		intron_variant	Intron 2 of 21	ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.59-185delA		intron_variant	Intron 2 of 21	2	NM_017868.4	ENSP00000433757.1

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

African (AFR) AF: 0.0401 AC: 787 AN: 19632

American (AMR) AF: 0.0118 AC: 83 AN: 7030

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 3 AN: 2082

East Asian (EAS) AF: 0.0258 AC: 52 AN: 2014

South Asian (SAS) AF: 0.0256 AC: 60 AN: 2344

European-Finnish (FIN) AF: 0.0227 AC: 80 AN: 3522

Middle Eastern (MID) AF: 0.00694 AC: 1 AN: 144

European-Non Finnish (NFE) AF: 0.00959 AC: 393 AN: 40978

Other (OTH) AF: 0.0102 AC: 11 AN: 1082

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34496236; hg19: chr11-113193824;