dbSNP rs4785686: SPG7:c.377-2543A>C (chr16-89521463-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003119.4(SPG7):c.377-2543A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,190 control chromosomes in the GnomAD database, including 15,820 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 15818 hom., cov: 34)

Exomes 𝑓: 0.50 ( 2 hom. )

Consequence

SPG7
NM_003119.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.407

Publications

12 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPG7	NM_003119.4 link	c.377-2543A>C		intron_variant	Intron 3 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.377-2543A>C		intron_variant	Intron 3 of 16		NM_003119.4	ENSP00000495795.2		Q9UQ90-1

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68545

AN:

152062

Hom.:

15801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.674

Gnomad SAS

AF:

0.565

Gnomad FIN

AF:

0.455

Gnomad MID

AF:

0.621

Gnomad NFE

AF:

0.456

Gnomad OTH

AF:

0.522

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Age Distribution

Exome Hom

Variant carriers

<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:

0.451

AC:

68603

AN:

152182

Hom.:

15818

Cov.:

AF XY:

0.456

AC XY:

33939

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.380

AC:

15764

AN:

41496

American (AMR)

AF:

0.483

AC:

7395

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.497

AC:

1725

AN:

3472

East Asian (EAS)

AF:

0.675

AC:

3493

AN:

5178

South Asian (SAS)

AF:

0.565

AC:

2728

AN:

4830

European-Finnish (FIN)

AF:

0.455

AC:

4818

AN:

10596

Middle Eastern (MID)

AF:

0.619

AC:

182

AN:

294

European-Non Finnish (NFE)

AF:

0.456

AC:

30974

AN:

67992

Other (OTH)

AF:

0.523

AC:

1107

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1985

3971

5956

7942

9927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.462

Hom.:

41734

Bravo

AF:

0.447

Asia WGS

AF:

0.611

AC:

2122

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.77

(source)

DANN

Benign

0.43

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over