chr3-78600286-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002941.4(ROBO1):​c.4768C>G​(p.Pro1590Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ROBO1
NM_002941.4 missense

Scores

6
10
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.88
Variant links:
Genes affected
ROBO1 (HGNC:10249): (roundabout guidance receptor 1) Bilateral symmetric nervous systems have special midline structures that establish a partition between the two mirror image halves. Some axons project toward and across the midline in response to long-range chemoattractants emanating from the midline. The product of this gene is a member of the immunoglobulin gene superfamily and encodes an integral membrane protein that functions in axon guidance and neuronal precursor cell migration. This receptor is activated by SLIT-family proteins, resulting in a repulsive effect on glioma cell guidance in the developing brain. A related gene is located at an adjacent region on chromosome 3. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ROBO1NM_002941.4 linkuse as main transcriptc.4768C>G p.Pro1590Ala missense_variant 30/31 ENST00000464233.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ROBO1ENST00000464233.6 linkuse as main transcriptc.4768C>G p.Pro1590Ala missense_variant 30/315 NM_002941.4 P3Q9Y6N7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.17
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.43
.;T;.;T;.;.
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D
M_CAP
Uncertain
0.22
D
MetaRNN
Pathogenic
0.77
D;D;D;D;D;D
MetaSVM
Uncertain
-0.082
T
MutationAssessor
Benign
0.90
.;L;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.70
T
PROVEAN
Pathogenic
-4.5
.;D;N;.;D;D
REVEL
Uncertain
0.52
Sift
Pathogenic
0.0
.;D;D;.;D;D
Sift4G
Uncertain
0.013
D;D;D;D;D;D
Polyphen
0.46
.;P;.;.;.;.
Vest4
0.87
MutPred
0.34
.;Loss of loop (P = 0.0203);.;.;.;.;
MVP
0.90
MPC
0.61
ClinPred
0.99
D
GERP RS
5.8
Varity_R
0.59
gMVP
0.17

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr3-78649436; API