rs1557211410
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_006014.5(LAGE3):c.188+1G>A variant causes a splice donor change involving the alteration of a non-conserved nucleotide. 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: 25)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
LAGE3
NM_006014.5 splice_donor
NM_006014.5 splice_donor
Scores
2
3
Splicing: ADA: 0.9999
1
Clinical Significance
Conservation
PhyloP100: 1.72
Genes affected
LAGE3 (HGNC:26058): (L antigen family member 3) This gene belongs to the ESO/LAGE gene family, members of which are clustered together on chromosome Xq28, and have similar exon-intron structures. Unlike the other family members which are normally expressed only in testis and activated in a wide range of human tumors, this gene is ubiquitously expressed in somatic tissues. The latter, combined with the finding that it is highly conserved in mouse and rat, suggests that the encoded protein is functionally important. An intronless pseudogene with high sequence similarity to this gene is located on chromosome 9. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease,
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-154478727-C-T is Pathogenic according to our data. Variant chrX-154478727-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 444873.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-154478727-C-T is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAGE3 | NM_006014.5 | c.188+1G>A | splice_donor_variant | ENST00000357360.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAGE3 | ENST00000357360.5 | c.188+1G>A | splice_donor_variant | 1 | NM_006014.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 25
GnomAD3 genomes
?
Cov.:
25
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 969542Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 299014
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
969542
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
299014
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 25
GnomAD4 genome
?
Cov.:
25
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Galloway-Mowat syndrome 2, X-linked Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 25, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
FATHMM_MKL
Benign
D
MutationTaster
Benign
D;D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at