11-113321802-G-T

Variant names:

• chr11-113321802-G-T
• rs1893699
• NM_017868.4:c.59-1486G>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.59-1486G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,970 control chromosomes in the GnomAD database, including 28,680 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 0.61 (28680 hom., cov: 32)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 4 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: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017868.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC12	NM_017868.4	MANE Select	c.59-1486G>T		intron	N/A	NP_060338.3
	TTC12	NM_001318533.2		c.59-1486G>T		intron	N/A	NP_001305462.1	J3KR69
	TTC12	NM_001378063.1		c.-17-1486G>T		intron	N/A	NP_001364992.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC12	ENST00000529221.6	TSL:2 MANE Select	c.59-1486G>T		intron	N/A	ENSP00000433757.1	Q9H892-1
	TTC12	ENST00000314756.7	TSL:1	c.59-1486G>T		intron	N/A	ENSP00000315160.3	Q9H892-2
	TTC12	ENST00000494714.5	TSL:1	n.59-1486G>T		intron	N/A	ENSP00000435291.1	Q9H892-2

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92890 AN: 151850 Hom.: 28676 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.644

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.612 AC: 92934 AN: 151970 Hom.: 28680 Cov.: 32 AF XY: 0.606 AC XY: 45004 AN XY: 74278

African (AFR) AF: 0.617 AC: 25551 AN: 41432

American (AMR) AF: 0.590 AC: 9018 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2201 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2498 AN: 5148

South Asian (SAS) AF: 0.610 AC: 2941 AN: 4820

European-Finnish (FIN) AF: 0.538 AC: 5655 AN: 10518

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.634 AC: 43086 AN: 67982

Other (OTH) AF: 0.613 AC: 1293 AN: 2108

Alfa AF: 0.567 Hom.: 2979

Bravo AF: 0.615

Asia WGS AF: 0.585 AC: 2035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.32
PhyloP100		0.11
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: rs1893699; hg19: chr11-113192524;