rs754672

Positions:

• chr11-113378414-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393020.5(TTC12):​c.1969-4963C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,092 control chromosomes in the GnomAD database, including 13,145 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 0.38 (13145 hom., cov: 32)
• Consequence: TTC12 ENST00000393020.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000393020.5	c.1969-4963C>T		intron_variant		5		ENSP00000376743

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57560 AN: 151974 Hom.: 13157 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.0560

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.378 AC: 57555 AN: 152092 Hom.: 13145 Cov.: 32 AF XY: 0.371 AC XY: 27583 AN XY: 74342

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.0555

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.430

Alfa AF: 0.509 Hom.: 24698

Bravo AF: 0.359

Asia WGS AF: 0.203 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs754672; hg19: chr11-113249136; COSMIC: COSV67514834;