Genetic Variant SPG11:p.Arg1530Ser (chr15-44595304-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_025137.4(SPG11):c.4590A>T(p.Arg1530Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. R1530T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SPG11
NM_025137.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.285

Publications

0 publications found

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]

SPG11 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 11
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Illumina, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
amyotrophic lateral sclerosis type 5
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Charcot-Marie-Tooth disease axonal type 2X
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
juvenile amyotrophic lateral sclerosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SPG11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31384015).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025137.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPG11	NM_025137.4	MANE Select	c.4590A>T	p.Arg1530Ser	missense	Exon 26 of 40	NP_079413.3
SPG11	NM_001411132.1		c.4590A>T	p.Arg1530Ser	missense	Exon 26 of 40	NP_001398061.1	A0A804HID9
SPG11	NM_001160227.2		c.4590A>T	p.Arg1530Ser	missense	Exon 26 of 38	NP_001153699.1	Q96JI7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPG11	ENST00000261866.12	TSL:1 MANE Select	c.4590A>T	p.Arg1530Ser	missense	Exon 26 of 40	ENSP00000261866.7	Q96JI7-1
SPG11	ENST00000535302.6	TSL:1	c.4590A>T	p.Arg1530Ser	missense	Exon 26 of 38	ENSP00000445278.2	Q96JI7-3
SPG11	ENST00000427534.6	TSL:1	c.4590A>T	p.Arg1530Ser	missense	Exon 26 of 37	ENSP00000396110.2	C4B7M2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

Eigen

Benign

-0.071

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.37

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.070

MetaRNN

Benign

0.31

MetaSVM

Uncertain

0.090

MutationAssessor

Uncertain

2.8

PhyloP100

-0.28

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.52

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.38

MutPred

0.36

Loss of MoRF binding (P = 0.0475)

MVP

0.66

MPC

0.26

ClinPred

0.97

GERP RS

-0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.39

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over