15-44567553-G-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_025137.4(SPG11):c.6625C>A(p.Arg2209Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SPG11
NM_025137.4 missense
NM_025137.4 missense
Scores
7
10
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 9.92
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 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 |
---|---|---|---|---|---|---|---|---|
SPG11 | NM_025137.4 | c.6625C>A | p.Arg2209Ser | missense_variant | Exon 36 of 40 | ENST00000261866.12 | NP_079413.3 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461832Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727226
GnomAD4 exome
AF:
AC:
3
AN:
1461832
Hom.:
Cov.:
34
AF XY:
AC XY:
2
AN XY:
727226
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;.;D;.
Vest4
MutPred
Gain of ubiquitination at K2208 (P = 0.0376);.;Gain of ubiquitination at K2208 (P = 0.0376);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at