Variant rs35932349 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_025137.4(SPG11):c.6330G>A(p.Gly2110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,614,046 control chromosomes in the GnomAD database, including 337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 55 hom., cov: 31)

Exomes 𝑓: 0.0099 ( 282 hom. )

Consequence

SPG11
NM_025137.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 0.566

Variant links:

Genes affected

SPG11 (HGNC:11226): (SPG11 vesicle trafficking associated, spatacsin) The protein encoded by this gene is a potential transmembrane protein that is phosphorylated upon DNA damage. Defects in this gene are a cause of spastic paraplegia type 11 (SPG11). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

SPG11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 15-44572696-C-T is Benign according to our data. Variant chr15-44572696-C-T is described in ClinVar as [Benign]. Clinvar id is 130367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-44572696-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.566 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPG11	NM_025137.4 linkuse as main transcript	c.6330G>A	p.Gly2110=	synonymous_variant	33/40	ENST00000261866.12	NP_079413.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPG11	ENST00000261866.12 linkuse as main transcript	c.6330G>A	p.Gly2110=	synonymous_variant	33/40	1	NM_025137.4	ENSP00000261866		Q96JI7-1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2178

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.00341

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.0969

Gnomad SAS

AF:

0.0429

Gnomad FIN

AF:

0.0353

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00543

Gnomad OTH

AF:

0.00910

GnomAD3 exomes

AF:

0.0180

AC:

4520

AN:

251470

Hom.:

123

AF XY:

0.0179

AC XY:

2432

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.00254

Gnomad ASJ exome

AF:

0.00675

Gnomad EAS exome

AF:

0.0944

Gnomad SAS exome

AF:

0.0328

Gnomad FIN exome

AF:

0.0329

Gnomad NFE exome

AF:

0.00512

Gnomad OTH exome

AF:

0.0138

GnomAD4 exome

AF:

0.00994

AC:

14529

AN:

1461882

Hom.:

282

Cov.:

AF XY:

0.0105

AC XY:

7650

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0158

Gnomad4 AMR exome

AF:

0.00291

Gnomad4 ASJ exome

AF:

0.00650

Gnomad4 EAS exome

AF:

0.0736

Gnomad4 SAS exome

AF:

0.0331

Gnomad4 FIN exome

AF:

0.0320

Gnomad4 NFE exome

AF:

0.00487

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.0144

AC:

2194

AN:

152164

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1288

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.0972

Gnomad4 SAS

AF:

0.0427

Gnomad4 FIN

AF:

0.0353

Gnomad4 NFE

AF:

0.00543

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00608

Hom.:

Bravo

AF:

0.0128

Asia WGS

AF:

0.0740

AC:

256

AN:

3478

EpiCase

AF:

0.00398

EpiControl

AF:

0.00492

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 25, 2016	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. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Hereditary spastic paraplegia 11

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 15, 2017	- -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Amyotrophic lateral sclerosis type 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

- -

Charcot-Marie-Tooth disease axonal type 2X

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

6.1

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over