rs863224924

Positions:

• chr16-89554501-GT-GCCAAGTCTGTA

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_003119.4(SPG7):​c.2120delTinsCCAAGTCTGTA​(p.Val707fs) variant causes a frameshift, missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as no classification for the single variant (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPG7 NM_003119.4 frameshift, missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.76

Genes affected

SPG7 (HGNC:11237): (SPG7 matrix AAA peptidase subunit, paraplegin) This gene encodes a mitochondrial metalloprotease protein that is a member of the AAA family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. Mutations in this gene cause autosomal recessive spastic paraplegia 7. Two transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPG7	NM_003119.4	c.2120delTinsCCAAGTCTGTA	p.Val707fs	frameshift_variant, missense_variant	16/17	ENST00000645818.2	NP_003110.1
SPG7	NM_001363850.1	c.2120delTinsCCAAGTCTGTA	p.Val707fs	frameshift_variant, missense_variant	16/18		NP_001350779.1
SPG7	XM_047434537.1	c.1247delTinsCCAAGTCTGTA	p.Val416fs	frameshift_variant, missense_variant	11/13		XP_047290493.1
SPG7	XM_047434540.1	c.806delTinsCCAAGTCTGTA	p.Val269fs	frameshift_variant, missense_variant	8/9		XP_047290496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000645818.2	c.2120delTinsCCAAGTCTGTA	p.Val707fs	frameshift_variant, missense_variant	16/17		NM_003119.4	ENSP00000495795.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

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: rs863224924; hg19: chr16-89620910;