16-89541827-A-G

Position:

• chr16-89541827-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003119.4(SPG7):​c.1325-2821A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,024 control chromosomes in the GnomAD database, including 31,337 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (31333 hom., cov: 32)
  • Exomes 𝑓: 0.71 (4 hom.)
• Consequence: SPG7 NM_003119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPG7	NM_003119.4	c.1325-2821A>G		intron_variant		ENST00000645818.2	NP_003110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000645818.2	c.1325-2821A>G		intron_variant			NM_003119.4	ENSP00000495795.2

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97329 AN: 151890 Hom.: 31291 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.714 AC: 10 AN: 14 Hom.: 4 Cov.: 0 AF XY: 0.750 AC XY: 9 AN XY: 12

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.700

GnomAD4 genome AF: 0.641 AC: 97424 AN: 152010 Hom.: 31333 Cov.: 32 AF XY: 0.642 AC XY: 47716 AN XY: 74316

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.590

Alfa AF: 0.627 Hom.: 32610

Bravo AF: 0.639

Asia WGS AF: 0.691 AC: 2400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.61

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: rs457372; hg19: chr16-89608235;