rs587777290
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1_StrongPP3_StrongPP5
The NM_173849.3(GSC):c.355+1G>C variant causes a splice donor change. In-silico tool predicts a pathogenic 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: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GSC
NM_173849.3 splice_donor
NM_173849.3 splice_donor
Scores
3
3
1
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 4.54
Genes affected
GSC (HGNC:4612): (goosecoid homeobox) This gene encodes a member of the bicoid subfamily of the paired (PRD) homeobox family of proteins. The encoded protein acts as a transcription factor and may be autoregulatory. A similar protein in mice plays a role in craniofacial and rib cage development during embryogenesis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.5839793 fraction of the gene.
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 14-94769660-C-G is Pathogenic according to our data. Variant chr14-94769660-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 126524.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSC | NM_173849.3 | c.355+1G>C | splice_donor_variant | ENST00000238558.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSC | ENST00000238558.5 | c.355+1G>C | splice_donor_variant | 1 | NM_173849.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1283452Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 629722
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1283452
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
629722
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 05, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D
GERP RS
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: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at