rs79201073

Variant names:

• chr16-89544791-G-A
• rs79201073
• NM_003119.4:c.1449+19G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-89544791-G-A
• chr16-89544791-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001363850.1(SPG7):​c.1449+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 1,613,508 control chromosomes in the GnomAD database, including 6,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.080 (663 hom., cov: 32)
  • Exomes 𝑓: 0.069 (5355 hom.)
• Consequence: SPG7 NM_001363850.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.718
• Publications: 7 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: Laboratory for Molecular Medicine, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-89544791-G-A is Benign according to our data. Variant chr16-89544791-G-A is described in ClinVar as Benign. ClinVar VariationId is 258907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363850.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPG7	NM_003119.4	MANE Select	c.1449+19G>A		intron	N/A	NP_003110.1
	SPG7	NM_001363850.1		c.1449+19G>A		intron	N/A	NP_001350779.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPG7	ENST00000645818.2	MANE Select	c.1449+19G>A		intron	N/A	ENSP00000495795.2
	SPG7	ENST00000268704.7	TSL:1	c.1428+19G>A		intron	N/A	ENSP00000268704.3
	SPG7	ENST00000918773.1		c.1539+19G>A		intron	N/A	ENSP00000588832.1

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12127 AN: 152166 Hom.: 663 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0937

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0842

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.0770

GnomAD2 exomes AF: 0.102 AC: 25603 AN: 250906 AF XY: 0.103

Gnomad AFR exome AF: 0.0662

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.325

Gnomad FIN exome AF: 0.0868

Gnomad NFE exome AF: 0.0584

Gnomad OTH exome AF: 0.0951

GnomAD4 exome AF: 0.0686 AC: 100226 AN: 1461224 Hom.: 5355 Cov.: 31 AF XY: 0.0709 AC XY: 51538 AN XY: 726888

African (AFR) AF: 0.0694 AC: 2321 AN: 33466

American (AMR) AF: 0.107 AC: 4777 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 2728 AN: 26128

East Asian (EAS) AF: 0.306 AC: 12149 AN: 39684

South Asian (SAS) AF: 0.150 AC: 12959 AN: 86242

European-Finnish (FIN) AF: 0.0854 AC: 4535 AN: 53120

Middle Eastern (MID) AF: 0.104 AC: 601 AN: 5764

European-Non Finnish (NFE) AF: 0.0496 AC: 55099 AN: 1111746

Other (OTH) AF: 0.0838 AC: 5057 AN: 60360

GnomAD4 genome AF: 0.0797 AC: 12143 AN: 152284 Hom.: 663 Cov.: 32 AF XY: 0.0851 AC XY: 6336 AN XY: 74464

African (AFR) AF: 0.0696 AC: 2893 AN: 41570

American (AMR) AF: 0.0937 AC: 1434 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3472

East Asian (EAS) AF: 0.312 AC: 1610 AN: 5166

South Asian (SAS) AF: 0.155 AC: 749 AN: 4820

European-Finnish (FIN) AF: 0.0842 AC: 894 AN: 10618

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0576 AC: 3916 AN: 68016

Other (OTH) AF: 0.0762 AC: 161 AN: 2112

Alfa AF: 0.0700 Hom.: 149

Bravo AF: 0.0798

Asia WGS AF: 0.213 AC: 740 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hereditary spastic paraplegia 7 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.61
DANN	Benign	0.63
PhyloP100		-0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs79201073; hg19: chr16-89611199; COSMIC: COSV107277036; COSMIC: COSV107277036;