11-113368747-G-A

Variant names:

• chr11-113368747-G-A
• rs2276446
• ENST00000314756.7:c.*120+284G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000314756.7(TTC12):​c.*120+284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000266 in 376,152 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TTC12 ENST00000314756.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260
• 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: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000270179 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000314756.7. 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	NR_165393.1		n.2027G>A		non_coding_transcript_exon	Exon 17 of 17
	TTC12	NR_147891.2		n.2370+284G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC12	ENST00000314756.7	TSL:1	c.*120+284G>A		intron	N/A	ENSP00000315160.3	Q9H892-2
	TTC12	ENST00000494714.5	TSL:1	n.*120+284G>A		intron	N/A	ENSP00000435291.1	Q9H892-2
	TTC12	ENST00000393020.5	TSL:5	c.1968+171G>A		intron	N/A	ENSP00000376743.1	A8MTE9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000266 AC: 1 AN: 376152 Hom.: 0 Cov.: 0 AF XY: 0.00000511 AC XY: 1 AN XY: 195734

African (AFR) AF: 0.00 AC: 0 AN: 11580

American (AMR) AF: 0.00 AC: 0 AN: 14316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12120

East Asian (EAS) AF: 0.00 AC: 0 AN: 28904

South Asian (SAS) AF: 0.00 AC: 0 AN: 30104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1760

European-Non Finnish (NFE) AF: 0.00000436 AC: 1 AN: 229582

Other (OTH) AF: 0.00 AC: 0 AN: 22528

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		-0.26

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: rs2276446;

hg19: chr11-113239469;