16-89508277-G-C

Position:

• chr16-89508277-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000646303.1(SPG7):​c.51+537G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 713,958 control chromosomes in the GnomAD database, including 74,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16651 hom., cov: 34)
  • Exomes 𝑓: 0.45 (57865 hom.)
• Consequence: SPG7 ENST00000646303.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.134

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-89508277-G-C is Benign according to our data. Variant chr16-89508277-G-C is described in ClinVar as [Benign]. Clinvar id is 1292099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC101927863	NR_188547.1	n.44C>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+537G>C		intron_variant				ENSP00000494160.1
SPG7	ENST00000647079.1	c.-225-2213G>C		intron_variant				ENSP00000495967.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70535 AN: 151954 Hom.: 16641 Cov.: 34

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.447 AC: 251170 AN: 561896 Hom.: 57865 Cov.: 8 AF XY: 0.449 AC XY: 123875 AN XY: 275658

Gnomad4 AFR exome AF: 0.429

Gnomad4 AMR exome AF: 0.455

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.703

Gnomad4 SAS exome AF: 0.547

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.428

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.464 AC: 70576 AN: 152062 Hom.: 16651 Cov.: 34 AF XY: 0.469 AC XY: 34868 AN XY: 74344

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.529

Alfa AF: 0.300 Hom.: 691

Bravo AF: 0.464

Asia WGS AF: 0.610 AC: 2106 AN: 3454

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.82
CADD	Benign	2.1
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9935289; hg19: chr16-89574685;