11-113379003-G-C

Variant names:

• chr11-113379003-G-C
• rs3897584
• ENST00000393020.5:c.1969-4374G>C

Variant summary

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

The ENST00000393020.5(TTC12):​c.1969-4374G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,110 control chromosomes in the GnomAD database, including 35,614 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 0.68 (35614 hom., cov: 32)
• Consequence: TTC12 ENST00000393020.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 9 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: G2P, Labcorp Genetics (formerly Invitae), 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393020.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC12	ENST00000393020.5	TSL:5	c.1969-4374G>C		intron	N/A	ENSP00000376743.1	A8MTE9

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103396 AN: 151992 Hom.: 35597 Cov.: 32

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.680 AC: 103458 AN: 152110 Hom.: 35614 Cov.: 32 AF XY: 0.676 AC XY: 50270 AN XY: 74342

African (AFR) AF: 0.777 AC: 32236 AN: 41494

American (AMR) AF: 0.582 AC: 8896 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2352 AN: 3472

East Asian (EAS) AF: 0.555 AC: 2867 AN: 5164

South Asian (SAS) AF: 0.591 AC: 2851 AN: 4822

European-Finnish (FIN) AF: 0.667 AC: 7052 AN: 10570

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44921 AN: 67986

Other (OTH) AF: 0.682 AC: 1441 AN: 2114

Alfa AF: 0.585 Hom.: 1836

Bravo AF: 0.677

Asia WGS AF: 0.555 AC: 1927 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.081
DANN	Benign	0.55
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3897584;

hg19: chr11-113249725;