16-89504227-T-C

Position:

• chr16-89504227-T-C

Variant summary

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

The ENST00000565623.1(ENSG00000261118):​n.234A>G variant causes a non coding transcript exon 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: ENST00000565623.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760

Genes affected

(HGNC:):

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC101927863	XR_007065184.1	n.3376A>G		non_coding_transcript_exon_variant	2/3
LOC101927863	XR_001752307.2	n.732A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000565623.1	n.234A>G		non_coding_transcript_exon_variant	1/2	2
SPG7	ENST00000647079.1	c.-225-6263T>C		intron_variant				ENSP00000495967

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78272 AN: 151982 Hom.: 20836 Cov.: 33

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: 7 AN: 10 Hom.: 2 Cov.: 0 AF XY: 0.700 AC XY: 7 AN XY: 10

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.515 AC: 78308 AN: 152096 Hom.: 20842 Cov.: 33 AF XY: 0.517 AC XY: 38441 AN XY: 74330

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.563

Alfa AF: 0.556 Hom.: 31653

Bravo AF: 0.504

Asia WGS AF: 0.615 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4347628; hg19: chr16-89570635;