rs4987094

Positions:

• chr11-113345201-G-A

Variant summary

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

The NM_017868.4(TTC12):​c.1154+761G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,192 control chromosomes in the GnomAD database, including 1,387 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 0.10 (1387 hom., cov: 32)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC12	NM_017868.4	c.1154+761G>A		intron_variant		ENST00000529221.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC12	ENST00000529221.6	c.1154+761G>A		intron_variant		2	NM_017868.4	A2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15807 AN: 152074 Hom.: 1387 Cov.: 32

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.0975

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

GnomAD4 genome AF: 0.104 AC: 15813 AN: 152192 Hom.: 1387 Cov.: 32 AF XY: 0.112 AC XY: 8326 AN XY: 74396

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0781

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.0950

Gnomad4 OTH AF: 0.0970

Alfa AF: 0.0926 Hom.: 820

Bravo AF: 0.0973

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs4987094; hg19: chr11-113215923;