chr15-44657182-G-A

Position:

• chr15-44657182-G-A

Variant summary

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

The NM_025137.4(SPG11):​c.782C>T​(p.Ser261Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPG11 NM_025137.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.95

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=0.22329083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPG11	NM_025137.4	c.782C>T	p.Ser261Leu	missense_variant	4/40	ENST00000261866.12	NP_079413.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG11	ENST00000261866.12	c.782C>T	p.Ser261Leu	missense_variant	4/40	1	NM_025137.4	ENSP00000261866

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;.;T;.;.
Eigen	Benign	0.059
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;M;.;M;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.071
Sift	Benign	0.16	T;T;T;T;T
Sift4G	Benign	0.20	T;T;T;D;D
Polyphen		0.023	B;.;B;.;.
Vest4		0.28
MutPred		0.38		Loss of disorder (P = 0.0105);Loss of disorder (P = 0.0105);Loss of disorder (P = 0.0105);Loss of disorder (P = 0.0105);Loss of disorder (P = 0.0105);
MVP		0.41
MPC		0.23
ClinPred		0.94	D
GERP RS		5.7
Varity_R		0.15
gMVP		0.30

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: chr15-44949380;