rs1553741312
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PP3_StrongPP5
The NM_018010.4(IFT57):c.777G>A(p.Lys259Lys) variant causes a splice region, synonymous change. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
IFT57
NM_018010.4 splice_region, synonymous
NM_018010.4 splice_region, synonymous
Scores
2
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 6.55
Publications
1 publications found
Genes affected
IFT57 (HGNC:17367): (intraflagellar transport 57) Predicted to enable DNA binding activity. Acts upstream of or within activation of cysteine-type endopeptidase activity involved in apoptotic process; apoptotic process; and regulation of apoptotic process. Predicted to be located in ciliary basal body. Predicted to be part of axoneme and intraciliary transport particle B. Predicted to be active in Golgi apparatus; centrosome; and cilium. Implicated in orofaciodigital syndrome. [provided by Alliance of Genome Resources, Apr 2022]
IFT57 Gene-Disease associations (from GenCC):
- orofaciodigital syndrome 18Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 5 ACMG points.
PP3
Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 3-108191521-C-T is Pathogenic according to our data. Variant chr3-108191521-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 506288.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| IFT57 | ENST00000264538.4 | c.777G>A | p.Lys259Lys | splice_region_variant, synonymous_variant | Exon 6 of 11 | 1 | NM_018010.4 | ENSP00000264538.3 | ||
| IFT57 | ENST00000478157.1 | n.*368G>A | splice_region_variant, non_coding_transcript_exon_variant | Exon 5 of 7 | 5 | ENSP00000417768.1 | ||||
| IFT57 | ENST00000478157.1 | n.*368G>A | 3_prime_UTR_variant | Exon 5 of 7 | 5 | ENSP00000417768.1 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 149950Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
0
AN:
149950
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000352 AC: 5AN: 1419328Hom.: 0 Cov.: 29 AF XY: 0.00000426 AC XY: 3AN XY: 705002 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
5
AN:
1419328
Hom.:
Cov.:
29
AF XY:
AC XY:
3
AN XY:
705002
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
31422
American (AMR)
AF:
AC:
1
AN:
37796
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25002
East Asian (EAS)
AF:
AC:
0
AN:
37976
South Asian (SAS)
AF:
AC:
1
AN:
77178
European-Finnish (FIN)
AF:
AC:
0
AN:
52674
Middle Eastern (MID)
AF:
AC:
0
AN:
5628
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1093110
Other (OTH)
AF:
AC:
0
AN:
58542
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00357191), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.345
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
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>80
Age
GnomAD4 genome 0.00 AC: 0AN: 149950Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 72958
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
149950
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
72958
African (AFR)
AF:
AC:
0
AN:
40710
American (AMR)
AF:
AC:
0
AN:
15018
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3460
East Asian (EAS)
AF:
AC:
0
AN:
5110
South Asian (SAS)
AF:
AC:
0
AN:
4774
European-Finnish (FIN)
AF:
AC:
0
AN:
9928
Middle Eastern (MID)
AF:
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67668
Other (OTH)
AF:
AC:
0
AN:
2058
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Orofaciodigital syndrome 18 Pathogenic:1
Aug 09, 2019
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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