rs11862081

Positions:

• chr16-89522080-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003119.4(SPG7):​c.377-1926A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,138 control chromosomes in the GnomAD database, including 14,779 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (14779 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SPG7 NM_003119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPG7	NM_003119.4	c.377-1926A>G		intron_variant		ENST00000645818.2	NP_003110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000645818.2	c.377-1926A>G		intron_variant			NM_003119.4	ENSP00000495795	P2

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65623 AN: 152018 Hom.: 14772 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.432 AC: 65650 AN: 152136 Hom.: 14779 Cov.: 33 AF XY: 0.438 AC XY: 32542 AN XY: 74364

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.508

Alfa AF: 0.456 Hom.: 15842

Bravo AF: 0.426

Asia WGS AF: 0.601 AC: 2089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.2
DANN	Benign	0.68

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: rs11862081; hg19: chr16-89588488;