chr11-113323597-A-AT

Variant names:

• chr11-113323597-A-AT
• rs142060645
• NM_017868.4:c.222+156dupT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_017868.4(TTC12):​c.222+156dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 510,946 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00092 (2 hom., cov: 29)
  • Exomes 𝑓: 0.0042 (0 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4	c.222+156dupT		intron_variant	Intron 3 of 21	ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.222+146_222+147insT		intron_variant	Intron 3 of 21	2	NM_017868.4	ENSP00000433757.1

Frequencies

GnomAD3 genomes AF: 0.000917 AC: 138 AN: 150422 Hom.: 2 Cov.: 29

Gnomad AFR AF: 0.00292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000889

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00421 AC: 1519 AN: 360414 Hom.: 0 AF XY: 0.00429 AC XY: 783 AN XY: 182724

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00940 AC: 86 AN: 9152

American (AMR) AF: 0.00569 AC: 55 AN: 9674

Ashkenazi Jewish (ASJ) AF: 0.00414 AC: 41 AN: 9904

East Asian (EAS) AF: 0.00439 AC: 102 AN: 23252

South Asian (SAS) AF: 0.00539 AC: 66 AN: 12238

European-Finnish (FIN) AF: 0.00409 AC: 92 AN: 22504

Middle Eastern (MID) AF: 0.00402 AC: 6 AN: 1492

European-Non Finnish (NFE) AF: 0.00387 AC: 976 AN: 251900

Other (OTH) AF: 0.00468 AC: 95 AN: 20298

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000923 AC: 139 AN: 150532 Hom.: 2 Cov.: 29 AF XY: 0.000925 AC XY: 68 AN XY: 73488

African (AFR) AF: 0.00293 AC: 120 AN: 40936

American (AMR) AF: 0.000530 AC: 8 AN: 15102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00105 AC: 5 AN: 4750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000889 AC: 6 AN: 67518

Other (OTH) AF: 0.00 AC: 0 AN: 2096

Alfa AF: 0.00 Hom.: 165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.98

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: rs142060645; hg19: chr11-113194319;