chr10-97004089-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_003061.3(SLIT1):c.3844G>A(p.Glu1282Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000348 in 1,611,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000038 ( 0 hom. )
Consequence
SLIT1
NM_003061.3 missense
NM_003061.3 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 4.92
Genes affected
SLIT1 (HGNC:11085): (slit guidance ligand 1) Enables Roundabout binding activity. Involved in axon extension involved in axon guidance; motor neuron axon guidance; and negative chemotaxis. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, SLIT1
BS2
?
High AC in GnomAdExome at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLIT1 | NM_003061.3 | c.3844G>A | p.Glu1282Lys | missense_variant | 34/37 | ENST00000266058.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLIT1 | ENST00000266058.9 | c.3844G>A | p.Glu1282Lys | missense_variant | 34/37 | 1 | NM_003061.3 | P1 | |
SLIT1 | ENST00000371070.8 | c.3844G>A | p.Glu1282Lys | missense_variant | 34/37 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152246Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251308Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135800
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GnomAD4 exome AF: 0.0000377 AC: 55AN: 1458772Hom.: 0 Cov.: 31 AF XY: 0.0000372 AC XY: 27AN XY: 725078
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152246Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74372
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 22, 2023 | The c.3844G>A (p.E1282K) alteration is located in exon 34 (coding exon 34) of the SLIT1 gene. This alteration results from a G to A substitution at nucleotide position 3844, causing the glutamic acid (E) at amino acid position 1282 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Gain of ubiquitination at E1282 (P = 0.0128);Gain of ubiquitination at E1282 (P = 0.0128);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at