16-89556997-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003119.4(SPG7):c.2292C>T(p.Ile764Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 1,613,830 control chromosomes in the GnomAD database, including 1,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 93 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1184 hom. )

Consequence

SPG7
NM_003119.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.20

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 16-89556997-C-T is Benign according to our data. Variant chr16-89556997-C-T is described in ClinVar as [Benign]. Clinvar id is 139250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89556997-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.2 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0281 (4274/152306) while in subpopulation NFE AF= 0.0409 (2781/68014). AF 95% confidence interval is 0.0396. There are 93 homozygotes in gnomad4. There are 1970 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 93 Mitochondrial gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPG7	NM_003119.4 link	c.2292C>T	p.Ile764Ile	synonymous_variant	Exon 17 of 17	ENST00000645818.2	NP_003110.1	Q9UQ90-1
SPG7	XM_047434540.1 link	c.978C>T	p.Ile326Ile	synonymous_variant	Exon 9 of 9		XP_047290496.1
SPG7	NM_001363850.1 link	c.*70C>T		3_prime_UTR_variant	Exon 18 of 18		NP_001350779.1
SPG7	XM_047434537.1 link	c.*70C>T		3_prime_UTR_variant	Exon 13 of 13		XP_047290493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000645818.2 link	c.2292C>T	p.Ile764Ile	synonymous_variant	Exon 17 of 17		NM_003119.4	ENSP00000495795.2		Q9UQ90-1

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4276

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.0923

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.0798

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.0156

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0409

Gnomad OTH

AF:

0.0406

GnomAD3 exomes

AF:

0.0287

AC:

7212

AN:

251238

Hom.:

144

AF XY:

0.0292

AC XY:

3971

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00843

Gnomad AMR exome

AF:

0.0188

Gnomad ASJ exome

AF:

0.0615

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00843

Gnomad FIN exome

AF:

0.0166

Gnomad NFE exome

AF:

0.0436

Gnomad OTH exome

AF:

0.0382

GnomAD4 exome

AF:

0.0378

AC:

55173

AN:

1461524

Hom.:

1184

Cov.:

AF XY:

0.0368

AC XY:

26774

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.00932

Gnomad4 AMR exome

AF:

0.0193

Gnomad4 ASJ exome

AF:

0.0646

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00883

Gnomad4 FIN exome

AF:

0.0187

Gnomad4 NFE exome

AF:

0.0433

Gnomad4 OTH exome

AF:

0.0369

GnomAD4 genome

AF:

0.0281

AC:

4274

AN:

152306

Hom.:

Cov.:

AF XY:

0.0265

AC XY:

1970

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.0239

Gnomad4 ASJ

AF:

0.0798

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00974

Gnomad4 FIN

AF:

0.0156

Gnomad4 NFE

AF:

0.0409

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0390

Hom.:

148

Bravo

AF:

0.0289

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0450

EpiControl

AF:

0.0420

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jul 06, 2012

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary spastic paraplegia 7

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 03, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary spastic paraplegia

Benign:1

Jan 20, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

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

-0.77

CADD

Benign

0.043

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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