rs2056309

chr16-89541006-G-Achr16-89541006-G-C

Variant summary

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

The NM_003119.4(SPG7):c.1325-3642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 448,870 control chromosomes in the GnomAD database, including 15,468 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 0.45 (15465 hom., cov: 29)
  • Exomes 𝑓: 0.000033 (3 hom.)
• Consequence: SPG7 NM_003119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.902

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPG7	NM_003119.4	c.1325-3642G>A		intron_variant		ENST00000645818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPG7	ENST00000645818.2	c.1325-3642G>A		intron_variant			NM_003119.4	P2

Frequencies

GnomAD3 genomes AF: 0.455 AC: 66923 AN: 147226 Hom.: 15456 Cov.: 29

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.0000332 AC: 10 AN: 301536 Hom.: 3 Cov.: 3 AF XY: 0.0000644 AC XY: 9 AN XY: 139646

Gnomad4 AFR exome AF: 0.000474

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000285

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.454 AC: 66946 AN: 147334 Hom.: 15465 Cov.: 29 AF XY: 0.455 AC XY: 32654 AN XY: 71708

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.511

Alfa AF: 0.431 Hom.: 11349

Bravo AF: 0.454

Asia WGS AF: 0.437 AC: 1276 AN: 2918

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.1
Dann	Benign	0.73

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: rs2056309; hg19: chr16-89607414;