rs312262714

chr15-44660445-GTCAATGAGCTTTTGCAATGCC-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM4 PP5_Moderate

The NM_025137.4(SPG11):c.408_428del(p.Glu136_Ile142del) variant causes a inframe deletion change. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPG11 NM_025137.4 inframe_deletion
• Clinical Significance: Pathogenic criteria provided, single submitter P:1 O:1
• Conservation: PhyloP100: 4.50

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 4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_025137.4.
• PP5: Variant 15-44660445-GTCAATGAGCTTTTGCAATGCC-G is Pathogenic according to our data. Variant chr15-44660445-GTCAATGAGCTTTTGCAATGCC-G is described in ClinVar as [Pathogenic]. Clinvar id is 41314.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPG11	NM_025137.4	c.408_428del	p.Glu136_Ile142del	inframe_deletion	2/40	ENST00000261866.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPG11	ENST00000261866.12	c.408_428del	p.Glu136_Ile142del	inframe_deletion	2/40	1	NM_025137.4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary spastic paraplegia Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Sep 14, 2023

Variant summary: SPG11 c.408_428del21 (p.Glu136_Ile142del) results in an in-frame deletion that is predicted to remove 7 amino acids from the encoded protein. The variant was absent in 251142 control chromosomes. c.408_428del21 has been reported in the literature in multiple individuals affected with Hereditary Spastic Paraplegia, Type 11, either at a homozygous state or at a compound heterozygous state along with second pathogenic variant(s) (example, Denora_2009, Vural_2021, Elert-Dobkowska_2019, Stromillo_2011). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 19105190, 30778698, 21625935, 33624863). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. -

Hereditary spastic paraplegia 11 Other:1

not provided, no classification provided

literature only

GeneReviews

-

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs312262714; hg19: chr15-44952643;