Genetic Variant ENST00000647079.1:c.-225-6263T>C (chr16-89504227-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000647079.1(SPG7):c.-225-6263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,106 control chromosomes in the GnomAD database, including 20,844 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 0.51 ( 20842 hom., cov: 33)

Exomes 𝑓: 0.70 ( 2 hom. )

Consequence

SPG7
ENST00000647079.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.760

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:

ENSG00000261118 (HGNC:):

ENSG00000261118 links:

Genome browser will be placed here

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=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000647079.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC101927863	NR_188547.1		n.467A>G		non_coding_transcript_exon	Exon 4 of 5
	LOC101927863	NR_188548.1		n.416A>G		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPG7	ENST00000647079.1		c.-225-6263T>C	intron	N/A	ENSP00000495967.1	A0A2R8Y726
ENSG00000261118	ENST00000565623.1	TSL:2	n.234A>G	non_coding_transcript_exon	Exon 1 of 2
ENSG00000261118	ENST00000726307.1		n.282A>G	non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

78272

AN:

151982

Hom.:

20836

Cov.:

show subpopulations

Gnomad AFR

AF:

0.378

Gnomad AMI

AF:

0.581

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.604

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.564

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.563

GnomAD4 exome

AF:

0.700

AC:

AN:

Hom.:

Cov.:

AF XY:

0.700

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)

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.515

AC:

78308

AN:

152096

Hom.:

20842

Cov.:

AF XY:

0.517

AC XY:

38441

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.378

AC:

15678

AN:

41500

American (AMR)

AF:

0.510

AC:

7793

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.604

AC:

2097

AN:

3470

East Asian (EAS)

AF:

0.668

AC:

3434

AN:

5142

South Asian (SAS)

AF:

0.570

AC:

2747

AN:

4820

European-Finnish (FIN)

AF:

0.564

AC:

5968

AN:

10588

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38683

AN:

67984

Other (OTH)

AF:

0.563

AC:

1190

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1975

3951

5926

7902

9877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.551

Hom.:

38725

Bravo

AF:

0.504

Asia WGS

AF:

0.615

AC:

2136

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.19

(source)

DANN

Benign

0.21

PhyloP100

-0.76

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over