3-129483544-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_052989.3(IFT122):c.1713G>T(p.Ser571Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,614,034 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S571S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.011 ( 12 hom., cov: 32)

Exomes 𝑓: 0.011 ( 152 hom. )

Consequence

IFT122
NM_052989.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.41

Publications

3 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:

ENSG00000299667 (HGNC:):

ENSG00000299667 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 3-129483544-G-T is Benign according to our data. Variant chr3-129483544-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 343243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.41 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.011 (1673/152174) while in subpopulation SAS AF = 0.0294 (141/4800). AF 95% confidence interval is 0.0254. There are 12 homozygotes in GnomAd4. There are 838 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT122	NM_052989.3 link	c.1713G>T	p.Ser571Ser	synonymous_variant	Exon 15 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.1713G>T	p.Ser571Ser	synonymous_variant	Exon 15 of 30	1	NM_052989.3	ENSP00000324005.4		Q9HBG6-1

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1669

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0291

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00868

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.0110

AC:

2757

AN:

251444

AF XY:

0.0122

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.00726

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.00982

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.0111

AC:

16179

AN:

1461860

Hom.:

152

Cov.:

AF XY:

0.0117

AC XY:

8481

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0160

AC:

534

AN:

33476

American (AMR)

AF:

0.00704

AC:

315

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00444

AC:

116

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.0304

AC:

2624

AN:

86254

European-Finnish (FIN)

AF:

0.00241

AC:

129

AN:

53420

Middle Eastern (MID)

AF:

0.0208

AC:

120

AN:

5766

European-Non Finnish (NFE)

AF:

0.0105

AC:

11686

AN:

1112000

Other (OTH)

AF:

0.0108

AC:

653

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

1019

2039

3058

4078

5097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.0110

AC:

1673

AN:

152174

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

838

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0145

AC:

604

AN:

41528

American (AMR)

AF:

0.0138

AC:

211

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.0294

AC:

141

AN:

4800

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00869

AC:

591

AN:

67992

Other (OTH)

AF:

0.0104

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

173

260

346

433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00430

Hom.:

Bravo

AF:

0.0119

EpiCase

AF:

0.00949

EpiControl

AF:

0.0113

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 13, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cranioectodermal dysplasia 1

Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Connective tissue disorder

Benign:1

Apr 22, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.012

(source)

DANN

Benign

0.66

PhyloP100

-2.4

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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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