NM_025137.4:c.5362G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025137.4(SPG11):​c.5362G>C​(p.Val1788Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1788M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

SPG11
NM_025137.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16
Variant links:
Genes affected
SPG11 (HGNC:11226): (SPG11 vesicle trafficking associated, spatacsin) The protein encoded by this gene is a potential transmembrane protein that is phosphorylated upon DNA damage. Defects in this gene are a cause of spastic paraplegia type 11 (SPG11). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.028085202).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPG11NM_025137.4 linkc.5362G>C p.Val1788Leu missense_variant Exon 30 of 40 ENST00000261866.12 NP_079413.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPG11ENST00000261866.12 linkc.5362G>C p.Val1788Leu missense_variant Exon 30 of 40 1 NM_025137.4 ENSP00000261866.7 Q96JI7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1458996
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
725526
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:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
12
DANN
Benign
0.79
DEOGEN2
Benign
0.014
T;.;T;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.62
T;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.028
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-1.2
N;N;.;N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.65
N;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.16
T;T;T;T
Sift4G
Benign
0.094
T;T;T;T
Polyphen
0.0
B;.;B;.
Vest4
0.029
MutPred
0.27
Loss of ubiquitination at K1793 (P = 0.1441);Loss of ubiquitination at K1793 (P = 0.1441);Loss of ubiquitination at K1793 (P = 0.1441);Loss of ubiquitination at K1793 (P = 0.1441);
MVP
0.35
MPC
0.036
ClinPred
0.30
T
GERP RS
2.9
Varity_R
0.044
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chr15-44876516; API