dbSNP rs111668739: IFT122:p.Gly1101Gly (chr3-129517506-G-T) – ACMG Classification: Benign (-21 pts)

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.3303G>T(p.Gly1101Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000942 in 1,613,986 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 4 hom. )

Consequence

IFT122
NM_052989.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0680

Publications

0 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 3-129517506-G-T is Benign according to our data. Variant chr3-129517506-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 343267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.068 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00504 (767/152318) while in subpopulation AFR AF = 0.0178 (740/41566). AF 95% confidence interval is 0.0167. There are 8 homozygotes in GnomAd4. There are 373 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052989.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFT122	NM_052989.3	MANE Select	c.3303G>T	p.Gly1101Gly	synonymous	Exon 27 of 30	NP_443715.1	Q9HBG6-1
IFT122	NM_052985.4		c.3456G>T	p.Gly1152Gly	synonymous	Exon 28 of 31	NP_443711.2	Q9HBG6-5
IFT122	NM_001410808.1		c.3306G>T	p.Gly1102Gly	synonymous	Exon 27 of 30	NP_001397737.1	A0A8I5KSG5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFT122	ENST00000348417.7	TSL:1 MANE Select	c.3303G>T	p.Gly1101Gly	synonymous	Exon 27 of 30	ENSP00000324005.4	Q9HBG6-1
IFT122	ENST00000296266.7	TSL:1	c.3456G>T	p.Gly1152Gly	synonymous	Exon 28 of 31	ENSP00000296266.3	Q9HBG6-5
IFT122	ENST00000507564.5	TSL:1	c.3282G>T	p.Gly1094Gly	synonymous	Exon 27 of 30	ENSP00000425536.1	Q9HBG6-6

Frequencies

GnomAD3 genomes

AF:

0.00504

AC:

767

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00136

AC:

341

AN:

251468

AF XY:

0.00104

show subpopulations

Gnomad AFR exome

AF:

0.0191

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000516

AC:

754

AN:

1461668

Hom.:

Cov.:

AF XY:

0.000476

AC XY:

346

AN XY:

727146

show subpopulations

African (AFR)

AF:

0.0183

AC:

613

AN:

33470

American (AMR)

AF:

0.000917

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1111882

Other (OTH)

AF:

0.00118

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

142

189

236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00504

AC:

767

AN:

152318

Hom.:

Cov.:

AF XY:

0.00501

AC XY:

373

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0178

AC:

740

AN:

41566

American (AMR)

AF:

0.00118

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68042

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

113

151

189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00217

Hom.:

Bravo

AF:

0.00564

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cranioectodermal dysplasia 1 (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.7

(source)

DANN

Benign

0.70

PhyloP100

0.068

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over