chr11-113323114-A-C

Variant names:

• chr11-113323114-A-C
• rs55939425
• NM_017868.4:c.59-174A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017868.4(TTC12):​c.59-174A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 151,540 control chromosomes in the GnomAD database, including 490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.065 (490 hom., cov: 31)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.319
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-113323114-A-C is Benign according to our data. Variant chr11-113323114-A-C is described in ClinVar as [Benign]. Clinvar id is 1250113.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4	c.59-174A>C		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.59-174A>C		intron_variant	Intron 2 of 21	2	NM_017868.4	ENSP00000433757.1

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9841 AN: 151426 Hom.: 490 Cov.: 31

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.0738

Gnomad AMR AF: 0.0302

Gnomad ASJ AF: 0.0900

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00582

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.0533

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

GnomAD4 genome AF: 0.0649 AC: 9842 AN: 151540 Hom.: 490 Cov.: 31 AF XY: 0.0641 AC XY: 4742 AN XY: 73980

African (AFR) AF: 0.0174 AC: 721 AN: 41454

American (AMR) AF: 0.0300 AC: 459 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0900 AC: 312 AN: 3468

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5172

South Asian (SAS) AF: 0.00604 AC: 29 AN: 4802

European-Finnish (FIN) AF: 0.137 AC: 1397 AN: 10166

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0992 AC: 6738 AN: 67894

Other (OTH) AF: 0.0527 AC: 111 AN: 2106

Alfa AF: 0.0861 Hom.: 112

Bravo AF: 0.0550

Asia WGS AF: 0.00809 AC: 29 AN: 3476

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.40
DANN	Benign	0.41
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs55939425; hg19: chr11-113193836;