rs463701

Positions:

• chr16-89532352-A-G
• chr16-89532352-A-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.1151-111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,316,676 control chromosomes in the GnomAD database, including 139,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16660 hom., cov: 33)
  • Exomes 𝑓: 0.45 (123027 hom.)
• Consequence: SPG7 NM_003119.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.383

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-89532352-A-G is Benign according to our data. Variant chr16-89532352-A-G is described in ClinVar as [Benign]. Clinvar id is 1221163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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	UniProt
SPG7	NM_003119.4	c.1151-111A>G		intron_variant		ENST00000645818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPG7	ENST00000645818.2	c.1151-111A>G		intron_variant			NM_003119.4	P2

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70553 AN: 151896 Hom.: 16634 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.453 AC: 527262 AN: 1164662 Hom.: 123027 AF XY: 0.458 AC XY: 271103 AN XY: 591516

Gnomad4 AFR exome AF: 0.438

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.506

Gnomad4 EAS exome AF: 0.690

Gnomad4 SAS exome AF: 0.558

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.432

Gnomad4 OTH exome AF: 0.482

GnomAD4 genome AF: 0.465 AC: 70621 AN: 152014 Hom.: 16660 Cov.: 33 AF XY: 0.469 AC XY: 34871 AN XY: 74310

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.529

Alfa AF: 0.463 Hom.: 21866

Bravo AF: 0.464

Asia WGS AF: 0.611 AC: 2123 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	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.29

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: rs463701; hg19: chr16-89598760;