16-89517401-C-T

Position:

• chr16-89517401-C-T

Variant summary

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

The NM_003119.4(SPG7):​c.376+4364C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 141,026 control chromosomes in the GnomAD database, including 14,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14138 hom., cov: 30)
  • Exomes 𝑓: 0.49 (13 hom.)
• Consequence: SPG7 NM_003119.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.969

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 -10 ACMG points.

• BP6: Variant 16-89517401-C-T is Benign according to our data. Variant chr16-89517401-C-T is described in ClinVar as [Benign]. Clinvar id is 1169989.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPG7	NM_003119.4	c.376+4364C>T		intron_variant		ENST00000645818.2	NP_003110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000645818.2	c.376+4364C>T		intron_variant			NM_003119.4	ENSP00000495795.2

Frequencies

GnomAD3 genomes AF: 0.423 AC: 59586 AN: 140830 Hom.: 14132 Cov.: 30

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.612

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.489 AC: 45 AN: 92 Hom.: 13 Cov.: 0 AF XY: 0.488 AC XY: 40 AN XY: 82

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.571

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.456

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.423 AC: 59606 AN: 140934 Hom.: 14138 Cov.: 30 AF XY: 0.428 AC XY: 29423 AN XY: 68710

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.497

Alfa AF: 0.454 Hom.: 15252

Bravo AF: 0.428

Asia WGS AF: 0.555 AC: 1770 AN: 3196

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary spastic paraplegia 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	22
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.67		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.67		Position offset: -2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8052076; hg19: chr16-89583809;