16-89530813-A-G

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.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

Publications

23 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: G2P, Orphanet, PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
autosomal dominant optic atrophy
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
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=-0.81).

BP6

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

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPG7	NM_003119.4	MANE Select	c.987+5A>G	splice_region intron	N/A	NP_003110.1	Q9UQ90-1
SPG7	NM_001363850.1		c.987+5A>G	splice_region intron	N/A	NP_001350779.1	A0A2R8Y3M4
SPG7	NM_199367.3		c.987+5A>G	splice_region intron	N/A	NP_955399.1	Q9UQ90-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPG7	ENST00000645818.2	MANE Select	c.987+5A>G	splice_region intron	N/A	ENSP00000495795.2	Q9UQ90-1
SPG7	ENST00000268704.7	TSL:1	c.987+5A>G	splice_region intron	N/A	ENSP00000268704.3	A0A2U3TZH1
SPG7	ENST00000341316.6	TSL:1	c.987+5A>G	splice_region intron	N/A	ENSP00000341157.2	Q9UQ90-2

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

GnomAD2 exomes

AF:

0.474

AC:

119186

AN:

251398

AF XY:

0.482

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 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

African (AFR)

AF:

0.423

AC:

14175

AN:

33472

American (AMR)

AF:

0.398

AC:

17805

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.506

AC:

13231

AN:

26134

East Asian (EAS)

AF:

0.689

AC:

27344

AN:

39694

South Asian (SAS)

AF:

0.560

AC:

48318

AN:

86240

European-Finnish (FIN)

AF:

0.449

AC:

23984

AN:

53408

Middle Eastern (MID)

AF:

0.574

AC:

3241

AN:

5648

European-Non Finnish (NFE)

AF:

0.428

AC:

476069

AN:

1111940

Other (OTH)

AF:

0.479

AC:

28914

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

22450

44900

67349

89799

112249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14434

28868

43302

57736

72170

<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:

0.460

AC:

69960

AN:

152004

Hom.:

16379

Cov.:

AF XY:

0.465

AC XY:

34520

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.420

AC:

17403

AN:

41450

American (AMR)

AF:

0.487

AC:

7430

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.497

AC:

1723

AN:

3470

East Asian (EAS)

AF:

0.672

AC:

3470

AN:

5160

South Asian (SAS)

AF:

0.566

AC:

2731

AN:

4824

European-Finnish (FIN)

AF:

0.448

AC:

4723

AN:

10540

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30771

AN:

67974

Other (OTH)

AF:

0.525

AC:

1108

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1986

3972

5959

7945

9931

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:

0.431

Hom.:

7271

Bravo

AF:

0.459

Asia WGS

AF:

0.615

AC:

2136

AN:

3478

EpiCase

AF:

0.475

EpiControl

AF:

0.475

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia 7 (6)

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=68/32

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over