16-89508168-G-A

Position:

• chr16-89508168-G-A

Variant summary

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

The ENST00000646303.1(SPG7):​c.51+428G>A 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 365,506 control chromosomes in the GnomAD database, including 39,403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14556 hom., cov: 33)
  • Exomes 𝑓: 0.47 (24847 hom.)
• Consequence: SPG7 ENST00000646303.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.217

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]

LOC101927863 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 16-89508168-G-A is Benign according to our data. Variant chr16-89508168-G-A is described in ClinVar as [Benign]. Clinvar id is 1261810.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC101927863	NR_188547.1	n.84+69C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000646303.1	c.51+428G>A		intron_variant				ENSP00000494160.1
SPG7	ENST00000647079.1	c.-225-2322G>A		intron_variant				ENSP00000495967.1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65105 AN: 151772 Hom.: 14551 Cov.: 33

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.504

GnomAD4 exome AF: 0.472 AC: 100770 AN: 213628 Hom.: 24847 Cov.: 2 AF XY: 0.474 AC XY: 51479 AN XY: 108622

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.501

Gnomad4 EAS exome AF: 0.698

Gnomad4 SAS exome AF: 0.537

Gnomad4 FIN exome AF: 0.443

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.471

GnomAD4 genome AF: 0.429 AC: 65126 AN: 151878 Hom.: 14556 Cov.: 33 AF XY: 0.434 AC XY: 32241 AN XY: 74218

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.505

Alfa AF: 0.456 Hom.: 13868

Bravo AF: 0.424

Asia WGS AF: 0.598 AC: 2069 AN: 3464

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 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.7
DANN	Benign	0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4785684; hg19: chr16-89574576;