rs1555364153
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PP2PP3_ModeratePP5_Moderate
The NM_015915.5(ATL1):c.563A>G(p.Gln188Arg) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q188H) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ATL1
NM_015915.5 missense
NM_015915.5 missense
Scores
11
6
1
Clinical Significance
Conservation
PhyloP100: 9.23
Genes affected
ATL1 (HGNC:11231): (atlastin GTPase 1) The protein encoded by this gene is a GTPase and a Golgi body transmembrane protein. The encoded protein can form a homotetramer and has been shown to interact with spastin and with mitogen-activated protein kinase kinase kinase kinase 4. This protein may be involved in axonal maintenance as evidenced by the fact that defects in this gene are a cause of spastic paraplegia type 3. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
?
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 8 uncertain in NM_015915.5
PP2
?
Missense variant where missense usually causes diseases, ATL1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.926
PP5
?
Variant 14-50593886-A-G is Pathogenic according to our data. Variant chr14-50593886-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 446867.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATL1 | NM_015915.5 | c.563A>G | p.Gln188Arg | missense_variant | 5/14 | ENST00000358385.12 | |
ATL1 | NM_001127713.1 | c.563A>G | p.Gln188Arg | missense_variant | 6/14 | ||
ATL1 | NM_181598.4 | c.563A>G | p.Gln188Arg | missense_variant | 5/13 | ||
ATL1 | XM_047431430.1 | c.563A>G | p.Gln188Arg | missense_variant | 6/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATL1 | ENST00000358385.12 | c.563A>G | p.Gln188Arg | missense_variant | 5/14 | 1 | NM_015915.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1454062Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 723824
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1454062
Hom.:
Cov.:
28
AF XY:
AC XY:
0
AN XY:
723824
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 22, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;.
Vest4
MutPred
Loss of disorder (P = 0.1437);Loss of disorder (P = 0.1437);.;
MVP
MPC
1.6
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at