rs8044175

Positions:

• chr16-89553289-G-T

Variant summary

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

The NM_003119.4(SPG7):​c.1936+154G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 859,084 control chromosomes in the GnomAD database, including 434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (281 hom., cov: 33)
  • Exomes 𝑓: 0.0059 (153 hom.)
• Consequence: SPG7 NM_003119.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.409

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 16-89553289-G-T is Benign according to our data. Variant chr16-89553289-G-T is described in ClinVar as [Benign]. Clinvar id is 677643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPG7	NM_003119.4	c.1936+154G>T		intron_variant		ENST00000645818.2
SPG7	NM_001363850.1	c.1936+154G>T		intron_variant
SPG7	XM_047434537.1	c.1063+154G>T		intron_variant
SPG7	XM_047434540.1	c.622+154G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPG7	ENST00000645818.2	c.1936+154G>T		intron_variant			NM_003119.4	P2

Frequencies

GnomAD3 genomes AF: 0.0353 AC: 5366 AN: 152182 Hom.: 272 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00237

Gnomad OTH AF: 0.0234

GnomAD4 exome AF: 0.00590 AC: 4168 AN: 706784 Hom.: 153 Cov.: 9 AF XY: 0.00516 AC XY: 1894 AN XY: 366982

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.00968

Gnomad4 ASJ exome AF: 0.00143

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00206

Gnomad4 FIN exome AF: 0.000509

Gnomad4 NFE exome AF: 0.00204

Gnomad4 OTH exome AF: 0.0120

GnomAD4 genome AF: 0.0355 AC: 5404 AN: 152300 Hom.: 281 Cov.: 33 AF XY: 0.0345 AC XY: 2569 AN XY: 74484

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00237

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0124 Hom.: 77

Bravo AF: 0.0411

Asia WGS AF: 0.0150 AC: 51 AN: 3478

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 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.47

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: rs8044175; hg19: chr16-89619697;