rs61740161

Positions:

chr3-129495459-G-A

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

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:5

Conservation

PhyloP100: 2.81

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 262270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-129495459-G-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
IFT122	NM_052989.3 linkuse as main transcript	c.2060G>A	p.Arg687Gln	missense_variant	18/30	ENST00000348417.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT122	ENST00000348417.7 linkuse as main transcript	c.2060G>A	p.Arg687Gln	missense_variant	18/30	1	NM_052989.3		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

GnomAD3 exomes

AF:

0.0769

AC:

19306

AN:

251098

Hom.:

200

AF XY:

0.0805

AC XY:

10926

AN XY:

135688

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 SAS exome

AF:

0.106

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

Gnomad4 AFR exome

AF:

0.0670

Gnomad4 AMR exome

AF:

0.0585

Gnomad4 ASJ exome

AF:

0.163

Gnomad4 EAS exome

AF:

0.0491

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.0382

Gnomad4 NFE exome

AF:

0.0849

Gnomad4 OTH exome

AF:

0.0918

GnomAD4 genome

AF:

0.0766

AC:

11654

AN:

152204

Hom.:

504

Cov.:

AF XY:

0.0759

AC XY:

5646

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0667

Gnomad4 AMR

AF:

0.0769

Gnomad4 ASJ

AF:

0.161

Gnomad4 EAS

AF:

0.0616

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.0381

Gnomad4 NFE

AF:

0.0833

Gnomad4 OTH

AF:

0.0965

Alfa

AF:

0.0803

Hom.:

106

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cranioectodermal dysplasia 1

Benign:2

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

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cranioectodermal dysplasia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 07, 2018

- -

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

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;.;.

MutationTaster

Benign

0.0013

P;P;P;P;P;P;P;P

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

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

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