rs3803680

Positions:

• chr16-89523835-G-A
• chr16-89523835-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003119.4(SPG7):​c.377-171G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 875,658 control chromosomes in the GnomAD database, including 95,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14799 hom., cov: 32)
  • Exomes 𝑓: 0.47 (81112 hom.)
• Consequence: SPG7 NM_003119.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.122

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]

SPG7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-89523835-G-A is Benign according to our data. Variant chr16-89523835-G-A is described in ClinVar as [Benign]. Clinvar id is 670124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89523835-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPG7	NM_003119.4	c.377-171G>A		intron_variant		ENST00000645818.2	NP_003110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000645818.2	c.377-171G>A		intron_variant			NM_003119.4	ENSP00000495795.2

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65673 AN: 151928 Hom.: 14791 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.507

GnomAD3 exomes AF: 0.477 AC: 67696 AN: 141940 Hom.: 16901 AF XY: 0.486 AC XY: 37040 AN XY: 76136

Gnomad AFR exome AF: 0.323

Gnomad AMR exome AF: 0.392

Gnomad ASJ exome AF: 0.516

Gnomad EAS exome AF: 0.681

Gnomad SAS exome AF: 0.563

Gnomad FIN exome AF: 0.455

Gnomad NFE exome AF: 0.455

Gnomad OTH exome AF: 0.505

GnomAD4 exome AF: 0.466 AC: 337504 AN: 723610 Hom.: 81112 Cov.: 10 AF XY: 0.473 AC XY: 180231 AN XY: 380724

Gnomad4 AFR exome AF: 0.327

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.509

Gnomad4 EAS exome AF: 0.695

Gnomad4 SAS exome AF: 0.558

Gnomad4 FIN exome AF: 0.459

Gnomad4 NFE exome AF: 0.445

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.432 AC: 65700 AN: 152048 Hom.: 14799 Cov.: 32 AF XY: 0.438 AC XY: 32559 AN XY: 74308

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.508

Alfa AF: 0.453 Hom.: 27898

Bravo AF: 0.427

Asia WGS AF: 0.602 AC: 2091 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.55
DANN	Benign	0.62

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: rs3803680; hg19: chr16-89590243;