3-129492134-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_052989.3(IFT122):c.1993-7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,604,430 control chromosomes in the GnomAD database, including 63,735 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 17995 hom., cov: 32)

Exomes 𝑓: 0.20 ( 45740 hom. )

Consequence

IFT122
NM_052989.3 splice_region, intron

Scores

Splicing: ADA: 0.00002742

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.306

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

cranioectodermal dysplasia 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
cranioectodermal dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IFT122 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-129492134-G-C is Benign according to our data. Variant chr3-129492134-G-C is described in ClinVar as Benign. ClinVar VariationId is 194901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT122	NM_052989.3 link	c.1993-7G>C		splice_region_variant, intron_variant	Intron 16 of 29	ENST00000348417.7	NP_443715.1	Q9HBG6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT122	ENST00000348417.7 link	c.1993-7G>C		splice_region_variant, intron_variant	Intron 16 of 29	1	NM_052989.3	ENSP00000324005.4		Q9HBG6-1

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

58054

AN:

151928

Hom.:

17931

Cov.:

show subpopulations

Gnomad AFR

AF:

0.827

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.0745

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.348

GnomAD2 exomes

AF:

0.282

AC:

70818

AN:

251436

AF XY:

0.272

show subpopulations

Gnomad AFR exome

AF:

0.841

Gnomad AMR exome

AF:

0.279

Gnomad ASJ exome

AF:

0.279

Gnomad EAS exome

AF:

0.676

Gnomad FIN exome

AF:

0.0704

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.203

AC:

295254

AN:

1452384

Hom.:

45740

Cov.:

AF XY:

0.207

AC XY:

149729

AN XY:

723160

show subpopulations

African (AFR)

AF:

0.854

AC:

28231

AN:

33062

American (AMR)

AF:

0.282

AC:

12591

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

7321

AN:

26036

East Asian (EAS)

AF:

0.661

AC:

26150

AN:

39574

South Asian (SAS)

AF:

0.372

AC:

31988

AN:

85960

European-Finnish (FIN)

AF:

0.0743

AC:

3965

AN:

53380

Middle Eastern (MID)

AF:

0.299

AC:

1713

AN:

5736

European-Non Finnish (NFE)

AF:

0.152

AC:

167935

AN:

1103950

Other (OTH)

AF:

0.256

AC:

15360

AN:

59970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

9544

19088

28632

38176

47720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6600

13200

19800

26400

33000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.383

AC:

58183

AN:

152046

Hom.:

17995

Cov.:

AF XY:

0.383

AC XY:

28431

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.827

AC:

34348

AN:

41518

American (AMR)

AF:

0.345

AC:

5269

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

998

AN:

3470

East Asian (EAS)

AF:

0.672

AC:

3462

AN:

5148

South Asian (SAS)

AF:

0.380

AC:

1831

AN:

4820

European-Finnish (FIN)

AF:

0.0745

AC:

786

AN:

10554

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.155

AC:

10512

AN:

67966

Other (OTH)

AF:

0.349

AC:

736

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1130

2259

3389

4518

5648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.161

Hom.:

827

Bravo

AF:

0.420

EpiCase

AF:

0.173

EpiControl

AF:

0.179

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 09, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 13, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Cranioectodermal dysplasia 1

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Cranioectodermal dysplasia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.7

(source)

DANN

Benign

0.57

PhyloP100

0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.010

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over