Genetic Variant SPG7:c.376+4364C>T (chr16-89517401-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.969

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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 rank	MANE	Protein	UniProt
SPG7	NM_003119.4 link	c.376+4364C>T		intron_variant	Intron 3 of 16	ENST00000645818.2	NP_003110.1	Q9UQ90-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000645818.2 link	c.376+4364C>T		intron_variant	Intron 3 of 16		NM_003119.4	ENSP00000495795.2		Q9UQ90-1

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

59586

AN:

140830

Hom.:

14132

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.488

AC XY:

AN XY:

show subpopulations

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.:

AF XY:

0.428

AC XY:

29423

AN XY:

68710

show subpopulations

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

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 7

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over