rs779161014

Positions:

• chr15-44585698-C-A
• chr15-44585698-C-G
• chr15-44585698-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025137.4(SPG11):​c.5059G>T​(p.Ala1687Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SPG11 NM_025137.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10912216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPG11	NM_025137.4	c.5059G>T	p.Ala1687Ser	missense_variant	29/40	ENST00000261866.12	NP_079413.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG11	ENST00000261866.12	c.5059G>T	p.Ala1687Ser	missense_variant	29/40	1	NM_025137.4	ENSP00000261866

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T;.;T;.
Eigen	Benign	-0.035
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.4	L;L;.;L
MutationTaster	Benign	0.98	N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.050	N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.47	T;T;T;T
Sift4G	Benign	0.77	T;T;T;T
Polyphen		0.51	P;.;P;.
Vest4		0.13
MutPred		0.33		Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);
MVP		0.62
MPC		0.048
ClinPred		0.30	T
GERP RS		5.5
Varity_R		0.017
gMVP		0.10

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

LitVar

Other links and lift over

dbSNP: rs779161014; hg19: chr15-44877896;