rs3922634

Variant names:

• chr16-89510358-T-C
• rs3922634
• NM_003119.4:c.184-132T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-89510358-T-C
• chr16-89510358-T-A
• chr16-89510358-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003119.4(SPG7):​c.184-132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 667,414 control chromosomes in the GnomAD database, including 76,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (15584 hom., cov: 32)
  • Exomes 𝑓: 0.48 (61164 hom.)
• Consequence: SPG7 NM_003119.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.348
• Publications: 17 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 16-89510358-T-C is Benign according to our data. Variant chr16-89510358-T-C is described in ClinVar as Benign. ClinVar VariationId is 1292102.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPG7	NM_003119.4	MANE Select	c.184-132T>C		intron	N/A	NP_003110.1	Q9UQ90-1
	SPG7	NM_001363850.1		c.184-132T>C		intron	N/A	NP_001350779.1	A0A2R8Y3M4
	SPG7	NM_199367.3		c.184-132T>C		intron	N/A	NP_955399.1	Q9UQ90-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPG7	ENST00000645818.2	MANE Select	c.184-132T>C		intron	N/A	ENSP00000495795.2	Q9UQ90-1
	SPG7	ENST00000268704.7	TSL:1	c.184-132T>C		intron	N/A	ENSP00000268704.3	A0A2U3TZH1
	SPG7	ENST00000341316.6	TSL:1	c.184-132T>C		intron	N/A	ENSP00000341157.2	Q9UQ90-2

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68004 AN: 151908 Hom.: 15568 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.520

GnomAD4 exome AF: 0.480 AC: 247467 AN: 515388 Hom.: 61164 AF XY: 0.486 AC XY: 135693 AN XY: 279440

African (AFR) AF: 0.387 AC: 5214 AN: 13482

American (AMR) AF: 0.420 AC: 10915 AN: 26016

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 9240 AN: 18160

East Asian (EAS) AF: 0.697 AC: 22143 AN: 31752

South Asian (SAS) AF: 0.556 AC: 30488 AN: 54844

European-Finnish (FIN) AF: 0.450 AC: 14325 AN: 31836

Middle Eastern (MID) AF: 0.556 AC: 1241 AN: 2234

European-Non Finnish (NFE) AF: 0.454 AC: 139862 AN: 308328

Other (OTH) AF: 0.489 AC: 14039 AN: 28736

GnomAD4 genome AF: 0.448 AC: 68056 AN: 152026 Hom.: 15584 Cov.: 32 AF XY: 0.453 AC XY: 33658 AN XY: 74328

African (AFR) AF: 0.378 AC: 15664 AN: 41444

American (AMR) AF: 0.483 AC: 7370 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1725 AN: 3470

East Asian (EAS) AF: 0.670 AC: 3474 AN: 5184

South Asian (SAS) AF: 0.564 AC: 2721 AN: 4822

European-Finnish (FIN) AF: 0.445 AC: 4697 AN: 10562

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30709 AN: 67978

Other (OTH) AF: 0.520 AC: 1099 AN: 2112

Alfa AF: 0.448 Hom.: 34457

Bravo AF: 0.446

Asia WGS AF: 0.611 AC: 2122 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.3
DANN	Benign	0.39
PhyloP100		0.35
PromoterAI		0.043	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3922634; hg19: chr16-89576766;