16-89510358-T-C

Position:

• chr16-89510358-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003119.4(SPG7):​c.184-132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 667,414 control chromosomes in the GnomAD database, including 76,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (15584 hom., cov: 32)
  • Exomes 𝑓: 0.48 (61164 hom.)
• Consequence: SPG7 NM_003119.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.348

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 16-89510358-T-C is Benign according to our data. Variant chr16-89510358-T-C is described in ClinVar as [Benign]. Clinvar id is 1292102.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPG7	NM_003119.4	c.184-132T>C		intron_variant		ENST00000645818.2	NP_003110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000645818.2	c.184-132T>C		intron_variant			NM_003119.4	ENSP00000495795.2

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68004 AN: 151908 Hom.: 15568 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.520

GnomAD4 exome AF: 0.480 AC: 247467 AN: 515388 Hom.: 61164 AF XY: 0.486 AC XY: 135693 AN XY: 279440

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.420

Gnomad4 ASJ exome AF: 0.509

Gnomad4 EAS exome AF: 0.697

Gnomad4 SAS exome AF: 0.556

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.489

GnomAD4 genome AF: 0.448 AC: 68056 AN: 152026 Hom.: 15584 Cov.: 32 AF XY: 0.453 AC XY: 33658 AN XY: 74328

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.520

Alfa AF: 0.452 Hom.: 18822

Bravo AF: 0.446

Asia WGS AF: 0.611 AC: 2122 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.3
DANN	Benign	0.39

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: rs3922634; hg19: chr16-89576766;