Variant 3-129476820-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_052989.3(IFT122):c.1147+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 1,613,730 control chromosomes in the GnomAD database, including 5,172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1300 hom., cov: 32)

Exomes 𝑓: 0.063 ( 3872 hom. )

Consequence

IFT122
NM_052989.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0220

Variant links:

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]

IFT122 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 3-129476820-C-T is Benign according to our data. Variant chr3-129476820-C-T is described in ClinVar as [Benign]. Clinvar id is 262267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-129476820-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT122	NM_052989.3 linkuse as main transcript	c.1147+19C>T		intron_variant		ENST00000348417.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT122	ENST00000348417.7 linkuse as main transcript	c.1147+19C>T		intron_variant		1	NM_052989.3		Q9HBG6-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16091

AN:

151996

Hom.:

1295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.0630

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.0300

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0549

Gnomad OTH

AF:

0.0934

GnomAD3 exomes

AF:

0.0750

AC:

18795

AN:

250692

Hom.:

1027

AF XY:

0.0736

AC XY:

9975

AN XY:

135520

show subpopulations

Gnomad AFR exome

AF:

0.223

Gnomad AMR exome

AF:

0.0339

Gnomad ASJ exome

AF:

0.105

Gnomad EAS exome

AF:

0.148

Gnomad SAS exome

AF:

0.0967

Gnomad FIN exome

AF:

0.0271

Gnomad NFE exome

AF:

0.0552

Gnomad OTH exome

AF:

0.0714

GnomAD4 exome

AF:

0.0630

AC:

92122

AN:

1461614

Hom.:

3872

Cov.:

AF XY:

0.0643

AC XY:

46778

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.232

Gnomad4 AMR exome

AF:

0.0361

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.0975

Gnomad4 FIN exome

AF:

0.0285

Gnomad4 NFE exome

AF:

0.0525

Gnomad4 OTH exome

AF:

0.0754

GnomAD4 genome

AF:

0.106

AC:

16124

AN:

152116

Hom.:

1300

Cov.:

AF XY:

0.105

AC XY:

7789

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.222

Gnomad4 AMR

AF:

0.0628

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.0300

Gnomad4 NFE

AF:

0.0549

Gnomad4 OTH

AF:

0.0929

Alfa

AF:

0.0631

Hom.:

604

Bravo

AF:

0.113

Asia WGS

AF:

0.109

AC:

380

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Cranioectodermal dysplasia 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.7

DANN

Benign

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over