rs61740161

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.2060G>A(p.Arg687Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 1,613,696 control chromosomes in the GnomAD database, including 5,995 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R687W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.077 ( 504 hom., cov: 32)

Exomes 𝑓: 0.085 ( 5491 hom. )

Consequence

IFT122
NM_052989.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.81

Publications

10 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 (MetaRNN=0.0018106997).

BP6

Variant 3-129495459-G-A is Benign according to our data. Variant chr3-129495459-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT122	NM_052989.3 link	c.2060G>A	p.Arg687Gln	missense_variant	Exon 18 of 30	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.2060G>A	p.Arg687Gln	missense_variant	Exon 18 of 30	1	NM_052989.3	ENSP00000324005.4		Q9HBG6-1

Frequencies

GnomAD3 genomes

AF:

0.0766

AC:

11645

AN:

152086

Hom.:

503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0667

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0770

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.0620

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0381

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0833

Gnomad OTH

AF:

0.0951

GnomAD2 exomes

AF:

0.0769

AC:

19306

AN:

251098

AF XY:

0.0805

show subpopulations

Gnomad AFR exome

AF:

0.0658

Gnomad AMR exome

AF:

0.0548

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.0602

Gnomad FIN exome

AF:

0.0354

Gnomad NFE exome

AF:

0.0806

Gnomad OTH exome

AF:

0.0933

GnomAD4 exome

AF:

0.0846

AC:

123666

AN:

1461492

Hom.:

5491

Cov.:

AF XY:

0.0864

AC XY:

62815

AN XY:

727042

show subpopulations

African (AFR)

AF:

0.0670

AC:

2243

AN:

33472

American (AMR)

AF:

0.0585

AC:

2614

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

4256

AN:

26132

East Asian (EAS)

AF:

0.0491

AC:

1951

AN:

39696

South Asian (SAS)

AF:

0.114

AC:

9847

AN:

86232

European-Finnish (FIN)

AF:

0.0382

AC:

2041

AN:

53406

Middle Eastern (MID)

AF:

0.128

AC:

737

AN:

5766

European-Non Finnish (NFE)

AF:

0.0849

AC:

94434

AN:

1111712

Other (OTH)

AF:

0.0918

AC:

5543

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

6508

13016

19524

26032

32540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3558

7116

10674

14232

17790

<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:

0.0766

AC:

11654

AN:

152204

Hom.:

504

Cov.:

AF XY:

0.0759

AC XY:

5646

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0667

AC:

2771

AN:

41534

American (AMR)

AF:

0.0769

AC:

1175

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

558

AN:

3470

East Asian (EAS)

AF:

0.0616

AC:

319

AN:

5178

South Asian (SAS)

AF:

0.104

AC:

503

AN:

4822

European-Finnish (FIN)

AF:

0.0381

AC:

404

AN:

10604

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0833

AC:

5667

AN:

68002

Other (OTH)

AF:

0.0965

AC:

204

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

543

1086

1630

2173

2716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0802

Hom.:

110

Bravo

AF:

0.0790

TwinsUK

AF:

0.0723

AC:

268

ALSPAC

AF:

0.0765

AC:

295

ESP6500AA

AF:

0.0651

AC:

287

ESP6500EA

AF:

0.0856

AC:

736

ExAC

AF:

0.0773

AC:

9390

Asia WGS

AF:

0.0980

AC:

343

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cranioectodermal dysplasia 1

Benign:2

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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cranioectodermal dysplasia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;.;.;.;.;.;.;T;T;T

Eigen

Benign

-0.071

Eigen_PC

Benign

0.046

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.90

D;D;D;D;D;D;D;D;D;D

MetaRNN

Benign

0.0018

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.4

.;.;.;.;.;.;.;L;.;.

PhyloP100

2.8

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.5

N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.21

T;T;T;T;T;T;T;D;T;T

Sift4G

Benign

0.25

T;T;T;T;T;T;T;T;T;T

Polyphen

0.020, 0.12

.;.;B;.;.;.;.;B;.;.

Vest4

0.26

MPC

0.26

ClinPred

0.013

GERP RS

3.4

Varity_R

0.054

gMVP

0.33

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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