16-89530813-A-G

Position:

chr16-89530813-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003119.4(SPG7):c.987+5A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 1,613,650 control chromosomes in the GnomAD database, including 165,563 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16379 hom., cov: 32)

Exomes 𝑓: 0.45 ( 149184 hom. )

Consequence

SPG7
NM_003119.4 splice_region, intron

Scores

Splicing: ADA: 0.0002255

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.239

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:

SPG7 (HGNC:):

SPG7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 16-89530813-A-G is Benign according to our data. Variant chr16-89530813-A-G is described in ClinVar as [Benign]. Clinvar id is 258911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89530813-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPG7	NM_003119.4 linkuse as main transcript	c.987+5A>G		splice_region_variant, intron_variant		ENST00000645818.2	NP_003110.1	Q9UQ90-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000645818.2 linkuse as main transcript	c.987+5A>G		splice_region_variant, intron_variant			NM_003119.4	ENSP00000495795.2		Q9UQ90-1

Frequencies

GnomAD3 genomes

AF:

0.460

AC:

69893

AN:

151886

Hom.:

16353

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.672

Gnomad SAS

AF:

0.566

Gnomad FIN

AF:

0.448

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.524

GnomAD3 exomes

AF:

0.474

AC:

119186

AN:

251398

Hom.:

29327

AF XY:

0.482

AC XY:

65541

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.422

Gnomad AMR exome

AF:

0.385

Gnomad ASJ exome

AF:

0.515

Gnomad EAS exome

AF:

0.677

Gnomad SAS exome

AF:

0.568

Gnomad FIN exome

AF:

0.445

Gnomad NFE exome

AF:

0.451

Gnomad OTH exome

AF:

0.499

GnomAD4 exome

AF:

0.447

AC:

653081

AN:

1461646

Hom.:

149184

Cov.:

AF XY:

0.452

AC XY:

328668

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.423

Gnomad4 AMR exome

AF:

0.398

Gnomad4 ASJ exome

AF:

0.506

Gnomad4 EAS exome

AF:

0.689

Gnomad4 SAS exome

AF:

0.560

Gnomad4 FIN exome

AF:

0.449

Gnomad4 NFE exome

AF:

0.428

Gnomad4 OTH exome

AF:

0.479

GnomAD4 genome

AF:

0.460

AC:

69960

AN:

152004

Hom.:

16379

Cov.:

AF XY:

0.465

AC XY:

34520

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.420

Gnomad4 AMR

AF:

0.487

Gnomad4 ASJ

AF:

0.497

Gnomad4 EAS

AF:

0.672

Gnomad4 SAS

AF:

0.566

Gnomad4 FIN

AF:

0.448

Gnomad4 NFE

AF:

0.453

Gnomad4 OTH

AF:

0.525

Alfa

AF:

0.426

Hom.:

6635

Bravo

AF:

0.459

Asia WGS

AF:

0.615

AC:

2136

AN:

3478

EpiCase

AF:

0.475

EpiControl

AF:

0.475

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 7

Benign:6

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Mar 27, 2017	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 14, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00023

dbscSNV1_RF

Benign

0.048

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