3-129430178-T-C

Variant names:

• chr3-129430178-T-C
• rs3138373
• ENST00000687461.1:n.145+360T>C

Variant summary

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

The ENST00000687461.1(IFT122):​n.145+360T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,196 control chromosomes in the GnomAD database, including 1,673 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 0.13 (1673 hom., cov: 33)
• Consequence: IFT122 ENST00000687461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

Genes affected

IFT122 (HGNC:13556): (intraflagellar transport 122) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This cytoplasmic protein contains seven WD repeats and an AF-2 domain which function by recruiting coregulatory molecules and in transcriptional activation. Mutations in this gene cause cranioectodermal dysplasia-1. A related pseudogene is located on chromosome 3. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT122	ENST00000687461.1	n.145+360T>C		intron_variant	Intron 1 of 30
IFT122	ENST00000693654.1	n.212+360T>C		intron_variant	Intron 1 of 29

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20002 AN: 152078 Hom.: 1668 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.132 AC: 20031 AN: 152196 Hom.: 1673 Cov.: 33 AF XY: 0.131 AC XY: 9765 AN XY: 74426

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0806

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.0397

Gnomad4 NFE AF: 0.0944

Gnomad4 OTH AF: 0.144

Alfa AF: 0.101 Hom.: 901

Bravo AF: 0.138

Asia WGS AF: 0.204 AC: 714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3138373; hg19: chr3-129149021;