ENST00000565623.1:n.234A>G

Variant names:

• chr16-89504227-T-C
• rs4347628
• ENST00000565623.1:n.234A>G

Variant summary

Our verdict is Benign. The variant received -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: ENSG00000261118 ENST00000565623.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760
• Publications: 23 publications found

Genes affected

ENSG00000261118 (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]

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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000565623.1. 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
	LOC101927863	NR_188547.1		n.467A>G		non_coding_transcript_exon	Exon 4 of 5
	LOC101927863	NR_188548.1		n.416A>G		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000261118	ENST00000565623.1	TSL:2	n.234A>G		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000261118	ENST00000726307.1		n.282A>G		non_coding_transcript_exon	Exon 3 of 4
	ENSG00000261118	ENST00000726308.1		n.146A>G		non_coding_transcript_exon	Exon 2 of 3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AF: 0.750 AC: 3 AN: 4

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

African (AFR) AF: 0.378 AC: 15678 AN: 41500

American (AMR) AF: 0.510 AC: 7793 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2097 AN: 3470

East Asian (EAS) AF: 0.668 AC: 3434 AN: 5142

South Asian (SAS) AF: 0.570 AC: 2747 AN: 4820

European-Finnish (FIN) AF: 0.564 AC: 5968 AN: 10588

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38683 AN: 67984

Other (OTH) AF: 0.563 AC: 1190 AN: 2112

Alfa AF: 0.551 Hom.: 38725

Bravo AF: 0.504

Asia WGS AF: 0.615 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.21
PhyloP100		-0.76

Splicing

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

Other links and lift over

dbSNP: rs4347628; hg19: chr16-89570635;