rs4785686

chr16-89521463-A-Cchr16-89521463-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.377-2543A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,190 control chromosomes in the GnomAD database, including 15,820 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 (15818 hom., cov: 34)
  • Exomes 𝑓: 0.50 (2 hom.)
• Consequence: SPG7 NM_003119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPG7	NM_003119.4	c.377-2543A>C		intron_variant		ENST00000645818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPG7	ENST00000645818.2	c.377-2543A>C		intron_variant			NM_003119.4	P2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68545 AN: 152062 Hom.: 15801 Cov.: 34

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.522

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.451 AC: 68603 AN: 152182 Hom.: 15818 Cov.: 34 AF XY: 0.456 AC XY: 33939 AN XY: 74412

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.523

Alfa AF: 0.468 Hom.: 30515

Bravo AF: 0.447

Asia WGS AF: 0.611 AC: 2122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.77
Dann	Benign	0.43

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: rs4785686; hg19: chr16-89587871;