NM_003061.3:c.288G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003061.3(SLIT1):​c.288G>C​(p.Gln96His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLIT1
NM_003061.3 missense

Scores

3
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.96
Variant links:
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]
ARHGAP19-SLIT1 (HGNC:48348): (ARHGAP19-SLIT1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring Rho GTPase activating protein 19 (ARHGAP19) and slit homolog 1 (SLIT1) genes on chromosome 10. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLIT1NM_003061.3 linkc.288G>C p.Gln96His missense_variant Exon 3 of 37 ENST00000266058.9 NP_003052.2 O75093-1A6H8V1
ARHGAP19-SLIT1NR_037909.1 linkn.1611G>C non_coding_transcript_exon_variant Exon 13 of 15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLIT1ENST00000266058.9 linkc.288G>C p.Gln96His missense_variant Exon 3 of 37 1 NM_003061.3 ENSP00000266058.4 O75093-1
ARHGAP19-SLIT1ENST00000479633.2 linkn.*11G>C non_coding_transcript_exon_variant Exon 13 of 15 2 ENSP00000473567.1
ARHGAP19-SLIT1ENST00000479633.2 linkn.*11G>C 3_prime_UTR_variant Exon 13 of 15 2 ENSP00000473567.1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461858
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.288G>C (p.Q96H) alteration is located in exon 3 (coding exon 3) of the SLIT1 gene. This alteration results from a G to C substitution at nucleotide position 288, causing the glutamine (Q) at amino acid position 96 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;T;T;T
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.87
D;D;D;D
M_CAP
Benign
0.043
D
MetaRNN
Uncertain
0.47
T;T;T;T
MetaSVM
Benign
-0.56
T
MutationAssessor
Benign
1.0
L;.;.;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-2.8
D;D;D;D
REVEL
Benign
0.24
Sift
Uncertain
0.020
D;D;D;D
Sift4G
Uncertain
0.037
D;D;.;D
Polyphen
0.98
D;.;.;.
Vest4
0.68
MutPred
0.27
Loss of loop (P = 0.2237);Loss of loop (P = 0.2237);.;Loss of loop (P = 0.2237);
MVP
0.71
MPC
1.2
ClinPred
0.99
D
GERP RS
5.2
Varity_R
0.50
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-98923190; API