chr15-44657156-C-G

Variant names:

• chr15-44657156-C-G
• NM_025137.4:c.808G>C

Variant summary

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

The NM_025137.4(SPG11):​c.808G>C​(p.Val270Leu) 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. 13/21 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. V270I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPG11 NM_025137.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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=0.18624479).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPG11	NM_025137.4	c.808G>C	p.Val270Leu	missense_variant	Exon 4 of 40	ENST00000261866.12	NP_079413.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPG11	ENST00000261866.12	c.808G>C	p.Val270Leu	missense_variant	Exon 4 of 40	1	NM_025137.4	ENSP00000261866.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T;.;T;.;.
Eigen	Benign	-0.023
Eigen_PC	Benign	-0.0071
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.83	T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.6	M;M;.;M;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.95	N;N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.024	D;D;D;D;D
Sift4G	Benign	0.22	T;T;T;D;D
Polyphen		0.40	B;.;P;.;.
Vest4		0.41
MutPred		0.25		Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);
MVP		0.36
MPC		0.24
ClinPred		0.80	D
GERP RS		5.7
Varity_R		0.15
gMVP		0.42

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: chr15-44949354;