16-89508187-C-CA

Position:

• chr16-89508187-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000646303.1(SPG7):​c.51+454dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (15480 hom., cov: 0)
  • Exomes 𝑓: 0.47 (24282 hom.)
• Consequence: SPG7 ENST00000646303.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.56

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 -10 ACMG points.

• BP6: Variant 16-89508187-C-CA is Benign according to our data. Variant chr16-89508187-C-CA is described in ClinVar as [Benign]. Clinvar id is 1228084.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
LOC101927863	NR_188547.1	n.84+49dupT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000646303.1	c.51+454dupA		intron_variant				ENSP00000494160.1
SPG7	ENST00000647079.1	c.-225-2296dupA		intron_variant				ENSP00000495967.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67723 AN: 151652 Hom.: 15466 Cov.: 0

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.518

GnomAD4 exome AF: 0.469 AC: 100476 AN: 214272 Hom.: 24282 Cov.: 3 AF XY: 0.470 AC XY: 51268 AN XY: 109092

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.691

Gnomad4 SAS exome AF: 0.516

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.474

GnomAD4 genome AF: 0.447 AC: 67767 AN: 151760 Hom.: 15480 Cov.: 0 AF XY: 0.451 AC XY: 33473 AN XY: 74150

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.518

Asia WGS AF: 0.604 AC: 2089 AN: 3460

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 14, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11383891; hg19: chr16-89574595;