rs267607193

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_052989.3(IFT122):​c.21G>C​(p.Trp7Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

IFT122
NM_052989.3 missense

Scores

10
7
2

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 6.07
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-129440351-G-C is Pathogenic according to our data. Variant chr3-129440351-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 4638.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IFT122NM_052989.3 linkuse as main transcriptc.21G>C p.Trp7Cys missense_variant 1/30 ENST00000348417.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IFT122ENST00000348417.7 linkuse as main transcriptc.21G>C p.Trp7Cys missense_variant 1/301 NM_052989.3 Q9HBG6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Cranioectodermal dysplasia 1 Pathogenic:1Other:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJun 11, 2010- -
not provided, no classification providedliterature onlyGeneReviews-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.29
CADD
Pathogenic
33
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.82
.;.;.;.;.;D
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.86
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.92
D;D;D;D;D;D
M_CAP
Benign
0.079
D
MetaRNN
Uncertain
0.61
D;D;D;D;D;D
MetaSVM
Uncertain
0.0087
D
MutationAssessor
Pathogenic
3.2
M;M;M;M;M;M
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-9.1
D;D;D;D;D;D
REVEL
Uncertain
0.47
Sift
Pathogenic
0.0
D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
1.0
D;.;.;.;.;D
Vest4
0.63
MutPred
0.61
Loss of catalytic residue at L5 (P = 0.004);Loss of catalytic residue at L5 (P = 0.004);Loss of catalytic residue at L5 (P = 0.004);Loss of catalytic residue at L5 (P = 0.004);Loss of catalytic residue at L5 (P = 0.004);Loss of catalytic residue at L5 (P = 0.004);
MVP
0.90
MPC
1.0
ClinPred
1.0
D
GERP RS
5.9
Varity_R
0.94
gMVP
0.77

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs267607193; hg19: chr3-129159194; API