chr10-97002959-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The NM_003061.3(SLIT1):c.3899G>A(p.Arg1300His) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
SLIT1
NM_003061.3 missense
NM_003061.3 missense
Scores
3
12
4
Clinical Significance
Conservation
PhyloP100: 5.03
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 -1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, SLIT1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.89
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLIT1 | NM_003061.3 | c.3899G>A | p.Arg1300His | missense_variant | 35/37 | ENST00000266058.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLIT1 | ENST00000266058.9 | c.3899G>A | p.Arg1300His | missense_variant | 35/37 | 1 | NM_003061.3 | P1 | |
SLIT1 | ENST00000371070.8 | c.3899G>A | p.Arg1300His | missense_variant | 35/37 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152200Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461720Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727160
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74346
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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 | Jul 27, 2021 | The c.3899G>A (p.R1300H) alteration is located in exon 35 (coding exon 35) of the SLIT1 gene. This alteration results from a G to A substitution at nucleotide position 3899, causing the arginine (R) at amino acid position 1300 to be replaced by a histidine (H). 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
Uncertain
D
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of catalytic residue at R1300 (P = 0.04);Loss of catalytic residue at R1300 (P = 0.04);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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