16-89508278-G-C

Position:

• chr16-89508278-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BS1 BS2_Supporting

The ENST00000646303.1(SPG7):​c.51+538G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 730,044 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00039 (2 hom.)
• Consequence: SPG7 ENST00000646303.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.198

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-89508278-G-C is Benign according to our data. Variant chr16-89508278-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1202937.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00378 (576/152192) while in subpopulation AFR AF= 0.0132 (547/41534). AF 95% confidence interval is 0.0123. There are 1 homozygotes in gnomad4. There are 263 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 Mitochondrial geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC101927863	NR_188547.1	n.43C>G		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000646303.1	c.51+538G>C		intron_variant				ENSP00000494160.1
SPG7	ENST00000647079.1	c.-225-2212G>C		intron_variant				ENSP00000495967.1

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 570 AN: 152084 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.000386 AC: 223 AN: 577852 Hom.: 2 Cov.: 8 AF XY: 0.000343 AC XY: 97 AN XY: 283158

Gnomad4 AFR exome AF: 0.0144

Gnomad4 AMR exome AF: 0.000584

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000465

Gnomad4 SAS exome AF: 0.0000649

Gnomad4 FIN exome AF: 0.0000897

Gnomad4 NFE exome AF: 0.00000868

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.00378 AC: 576 AN: 152192 Hom.: 1 Cov.: 33 AF XY: 0.00353 AC XY: 263 AN XY: 74408

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000210 Hom.: 0

Bravo AF: 0.00447

Asia WGS AF: 0.00145 AC: 5 AN: 3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs539811230; hg19: chr16-89574686;