rs3803679

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003119.4(SPG7):c.618+12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,604,872 control chromosomes in the GnomAD database, including 165,514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16468 hom., cov: 30)

Exomes 𝑓: 0.45 ( 149046 hom. )

Consequence

SPG7
NM_003119.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.28

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 7
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SPG7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 16-89524259-T-C is Benign according to our data. Variant chr16-89524259-T-C is described in ClinVar as Benign. ClinVar VariationId is 258910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPG7	NM_003119.4 link	c.618+12T>C		intron_variant	Intron 4 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.618+12T>C		intron_variant	Intron 4 of 16		NM_003119.4	ENSP00000495795.2		Q9UQ90-1

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70002

AN:

151138

Hom.:

16443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.672

Gnomad SAS

AF:

0.566

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.621

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.526

GnomAD2 exomes

AF:

0.475

AC:

117836

AN:

247950

AF XY:

0.484

show subpopulations

Gnomad AFR exome

AF:

0.424

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.517

Gnomad EAS exome

AF:

0.677

Gnomad FIN exome

AF:

0.452

Gnomad NFE exome

AF:

0.452

Gnomad OTH exome

AF:

0.499

GnomAD4 exome

AF:

0.448

AC:

651194

AN:

1453616

Hom.:

149046

Cov.:

AF XY:

0.453

AC XY:

327182

AN XY:

722100

show subpopulations

African (AFR)

AF:

0.432

AC:

14291

AN:

33092

American (AMR)

AF:

0.395

AC:

17623

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

13163

AN:

25916

East Asian (EAS)

AF:

0.689

AC:

27270

AN:

39560

South Asian (SAS)

AF:

0.560

AC:

48114

AN:

85938

European-Finnish (FIN)

AF:

0.456

AC:

23825

AN:

52304

Middle Eastern (MID)

AF:

0.561

AC:

2533

AN:

4512

European-Non Finnish (NFE)

AF:

0.429

AC:

475636

AN:

1107728

Other (OTH)

AF:

0.479

AC:

28739

AN:

59964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

19115

38230

57344

76459

95574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14456

28912

43368

57824

72280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.463

AC:

70070

AN:

151256

Hom.:

16468

Cov.:

AF XY:

0.468

AC XY:

34558

AN XY:

73900

show subpopulations

African (AFR)

AF:

0.427

AC:

17499

AN:

40974

American (AMR)

AF:

0.487

AC:

7408

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.497

AC:

1722

AN:

3464

East Asian (EAS)

AF:

0.672

AC:

3447

AN:

5128

South Asian (SAS)

AF:

0.566

AC:

2711

AN:

4790

European-Finnish (FIN)

AF:

0.456

AC:

4793

AN:

10516

Middle Eastern (MID)

AF:

0.627

AC:

183

AN:

292

European-Non Finnish (NFE)

AF:

0.454

AC:

30788

AN:

67876

Other (OTH)

AF:

0.527

AC:

1107

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1902

3803

5705

7606

9508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.465

Hom.:

3055

Bravo

AF:

0.461

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 7

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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. -

Mar 27, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

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

-0.93

CADD

Benign

0.086

(source)

DANN

Benign

0.17

PhyloP100

-1.3

PromoterAI

-0.00030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over