rs755938967
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PM2PP3_ModeratePP5
The NM_152558.5(IQCE):c.395-1G>A variant causes a splice acceptor change. The variant allele was found at a frequency of 0.0000142 in 1,409,898 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
IQCE
NM_152558.5 splice_acceptor
NM_152558.5 splice_acceptor
Scores
4
2
1
Splicing: ADA: 0.9999
2
Clinical Significance
Conservation
PhyloP100: 6.39
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 4, offset of 1, new splice context is: tttgtttatgtttctctaAGtca. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 7-2573417-G-A is Pathogenic according to our data. Variant chr7-2573417-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 437834.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-2573417-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IQCE | NM_152558.5 | c.395-1G>A | splice_acceptor_variant | ENST00000402050.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQCE | ENST00000402050.7 | c.395-1G>A | splice_acceptor_variant | 1 | NM_152558.5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152118Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000164 AC: 4AN: 243892Hom.: 0 AF XY: 0.00000755 AC XY: 1AN XY: 132526
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GnomAD4 exome AF: 0.0000143 AC: 18AN: 1257780Hom.: 0 Cov.: 18 AF XY: 0.0000189 AC XY: 12AN XY: 636248
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152118Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74322
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Polydactyly, postaxial, type a7 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 10, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D;D;D;D
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at