dbSNP rs187330648: SPG7:p.Gly40Gly (chr16-89508537-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003119.4(SPG7):c.120G>A(p.Gly40Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,512,498 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 12 hom., cov: 33)

Exomes 𝑓: 0.013 ( 126 hom. )

Consequence

SPG7
NM_003119.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:7

Conservation

PhyloP100: 1.29

Publications

2 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:

ENSG00000261118 (HGNC:):

ENSG00000261118 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 16-89508537-G-A is Benign according to our data. Variant chr16-89508537-G-A is described in ClinVar as Benign. ClinVar VariationId is 139253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.29 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00936 (1426/152290) while in subpopulation NFE AF = 0.0146 (992/67992). AF 95% confidence interval is 0.0138. There are 12 homozygotes in GnomAd4. There are 644 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 AD,AR gene

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	HGVSp	Effect	Exon Rank	Protein	UniProt
SPG7	NM_003119.4	MANE Select	c.120G>A	p.Gly40Gly	synonymous	Exon 1 of 17	NP_003110.1	Q9UQ90-1
SPG7	NM_001363850.1		c.120G>A	p.Gly40Gly	synonymous	Exon 1 of 18	NP_001350779.1	A0A2R8Y3M4
SPG7	NM_199367.3		c.120G>A	p.Gly40Gly	synonymous	Exon 1 of 10	NP_955399.1	Q9UQ90-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPG7	ENST00000645818.2	MANE Select	c.120G>A	p.Gly40Gly	synonymous	Exon 1 of 17	ENSP00000495795.2	Q9UQ90-1
SPG7	ENST00000268704.7	TSL:1	c.120G>A	p.Gly40Gly	synonymous	Exon 1 of 17	ENSP00000268704.3	A0A2U3TZH1
SPG7	ENST00000341316.6	TSL:1	c.120G>A	p.Gly40Gly	synonymous	Exon 1 of 10	ENSP00000341157.2	Q9UQ90-2

Frequencies

GnomAD3 genomes

AF:

0.00937

AC:

1426

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00294

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0146

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00974

AC:

1044

AN:

107214

AF XY:

0.00969

show subpopulations

Gnomad AFR exome

AF:

0.00304

Gnomad AMR exome

AF:

0.00830

Gnomad ASJ exome

AF:

0.00909

Gnomad EAS exome

AF:

0.000279

Gnomad FIN exome

AF:

0.00263

Gnomad NFE exome

AF:

0.0156

Gnomad OTH exome

AF:

0.00947

GnomAD4 exome

AF:

0.0127

AC:

17289

AN:

1360208

Hom.:

126

Cov.:

AF XY:

0.0125

AC XY:

8400

AN XY:

670778

show subpopulations

African (AFR)

AF:

0.00191

AC:

AN:

27768

American (AMR)

AF:

0.00888

AC:

296

AN:

33336

Ashkenazi Jewish (ASJ)

AF:

0.00884

AC:

213

AN:

24098

East Asian (EAS)

AF:

0.0000613

AC:

AN:

32648

South Asian (SAS)

AF:

0.00671

AC:

514

AN:

76598

European-Finnish (FIN)

AF:

0.00338

AC:

126

AN:

37248

Middle Eastern (MID)

AF:

0.0119

AC:

AN:

4040

European-Non Finnish (NFE)

AF:

0.0145

AC:

15462

AN:

1067904

Other (OTH)

AF:

0.0102

AC:

575

AN:

56568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

896

1792

2687

3583

4479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

582

1164

1746

2328

2910

<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:

0.00936

AC:

1426

AN:

152290

Hom.:

Cov.:

AF XY:

0.00865

AC XY:

644

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00293

AC:

122

AN:

41586

American (AMR)

AF:

0.0127

AC:

195

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00476

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00236

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0146

AC:

992

AN:

67992

Other (OTH)

AF:

0.0151

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

153

230

306

383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00509

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00116

AC:

AN:

3466

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia 7 (3)

not specified (3)

Hereditary spastic paraplegia (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.9

(source)

DANN

Benign

0.83

PhyloP100

1.3

PromoterAI

-0.00070

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism

(source)

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

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