16-89549357-T-G

Variant names:

• chr16-89549357-T-G
• rs2019604
• NM_003119.4:c.1664-1137T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003119.4(SPG7):​c.1664-1137T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 390,954 control chromosomes in the GnomAD database, including 4,049 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 0.12 (1307 hom., cov: 33)
  • Exomes 𝑓: 0.14 (2742 hom.)
• Consequence: SPG7 NM_003119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPG7	NM_003119.4	c.1664-1137T>G		intron_variant	Intron 12 of 16	ENST00000645818.2	NP_003110.1
SPG7	NM_001363850.1	c.1664-1137T>G		intron_variant	Intron 12 of 17		NP_001350779.1
SPG7	XM_047434537.1	c.791-1137T>G		intron_variant	Intron 7 of 12		XP_047290493.1
SPG7	XM_047434540.1	c.350-1137T>G		intron_variant	Intron 4 of 8		XP_047290496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000645818.2	c.1664-1137T>G		intron_variant	Intron 12 of 16		NM_003119.4	ENSP00000495795.2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18209 AN: 152132 Hom.: 1303 Cov.: 33

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.152

GnomAD3 exomes AF: 0.139 AC: 11984 AN: 86048 Hom.: 935 AF XY: 0.144 AC XY: 6416 AN XY: 44440

Gnomad AFR exome AF: 0.0510

Gnomad AMR exome AF: 0.0952

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.142

Gnomad FIN exome AF: 0.0805

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.145 AC: 34538 AN: 238704 Hom.: 2742 Cov.: 0 AF XY: 0.145 AC XY: 19377 AN XY: 133352

Gnomad4 AFR exome AF: 0.0543

Gnomad4 AMR exome AF: 0.0897

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.0811

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.120 AC: 18222 AN: 152250 Hom.: 1307 Cov.: 33 AF XY: 0.115 AC XY: 8573 AN XY: 74458

Gnomad4 AFR AF: 0.0569

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.153

Alfa AF: 0.138 Hom.: 1044

Bravo AF: 0.120

Asia WGS AF: 0.110 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.80

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: rs2019604; hg19: chr16-89615765; COSMIC: COSV51950225; COSMIC: COSV51950225;