16-89537178-A-G

Position:

• chr16-89537178-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000341316.6(SPG7):​c.*268A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 1,445,254 control chromosomes in the GnomAD database, including 148,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17155 hom., cov: 32)
  • Exomes 𝑓: 0.45 (130950 hom.)
• Consequence: SPG7 ENST00000341316.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0250

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 16-89537178-A-G is Benign according to our data. Variant chr16-89537178-A-G is described in ClinVar as [Benign]. Clinvar id is 684094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPG7	NM_003119.4	c.1324+4542A>G		intron_variant		ENST00000645818.2	NP_003110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000645818.2	c.1324+4542A>G		intron_variant			NM_003119.4	ENSP00000495795	P2

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71632 AN: 151892 Hom.: 17138 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.446 AC: 576290 AN: 1293244 Hom.: 130950 Cov.: 38 AF XY: 0.450 AC XY: 282655 AN XY: 628626

Gnomad4 AFR exome AF: 0.465

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.505

Gnomad4 EAS exome AF: 0.693

Gnomad4 SAS exome AF: 0.562

Gnomad4 FIN exome AF: 0.454

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.472 AC: 71685 AN: 152010 Hom.: 17155 Cov.: 32 AF XY: 0.476 AC XY: 35366 AN XY: 74292

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.533

Alfa AF: 0.463 Hom.: 23457

Bravo AF: 0.472

Asia WGS AF: 0.613 AC: 2130 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.0
DANN	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs382745; hg19: chr16-89603586;