11-113328424-C-T

Variant names:

• chr11-113328424-C-T
• rs10502172
• NM_017868.4:c.445-1496C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017868.4(TTC12):​c.445-1496C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,026 control chromosomes in the GnomAD database, including 10,857 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (10857 hom., cov: 32)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.990
• Publications: 29 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4	c.445-1496C>T		intron_variant	Intron 6 of 21	ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.445-1496C>T		intron_variant	Intron 6 of 21	2	NM_017868.4	ENSP00000433757.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50366 AN: 151908 Hom.: 10868 Cov.: 32

Gnomad AFR AF: 0.0862

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.0513

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.331 AC: 50345 AN: 152026 Hom.: 10857 Cov.: 32 AF XY: 0.327 AC XY: 24326 AN XY: 74324

African (AFR) AF: 0.0860 AC: 3566 AN: 41472

American (AMR) AF: 0.287 AC: 4384 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1686 AN: 3470

East Asian (EAS) AF: 0.0508 AC: 263 AN: 5176

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4824

European-Finnish (FIN) AF: 0.447 AC: 4708 AN: 10536

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32876 AN: 67964

Other (OTH) AF: 0.373 AC: 786 AN: 2110

Alfa AF: 0.453 Hom.: 25090

Bravo AF: 0.307

Asia WGS AF: 0.170 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.61
PhyloP100		-0.99
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: rs10502172; hg19: chr11-113199146;