rs80338869

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_025137.4(SPG11):c.7023C>T(p.Tyr2341Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 1,613,970 control chromosomes in the GnomAD database, including 655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.019 ( 31 hom., cov: 32)

Exomes 𝑓: 0.026 ( 624 hom. )

Consequence

SPG11
NM_025137.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: 1.05

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 -9 ACMG points.

BP6

Variant 15-44564675-G-A is Benign according to our data. Variant chr15-44564675-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 41357.We mark this variant Likely_benign, oryginal submissions are: {Benign=4, Uncertain_significance=1}. Variant chr15-44564675-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0189 (2878/152250) while in subpopulation NFE AF= 0.0286 (1944/68014). AF 95% confidence interval is 0.0275. There are 31 homozygotes in gnomad4. There are 1309 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPG11	NM_025137.4 link	c.7023C>T	p.Tyr2341Tyr	synonymous_variant	Exon 39 of 40	ENST00000261866.12	NP_079413.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPG11	ENST00000261866.12 link	c.7023C>T	p.Tyr2341Tyr	synonymous_variant	Exon 39 of 40	1	NM_025137.4	ENSP00000261866.7		Q96JI7-1

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2879

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00519

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.00387

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0286

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0205

AC:

5158

AN:

251064

Hom.:

AF XY:

0.0209

AC XY:

2837

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.00490

Gnomad AMR exome

AF:

0.0200

Gnomad ASJ exome

AF:

0.0317

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0167

Gnomad FIN exome

AF:

0.00471

Gnomad NFE exome

AF:

0.0288

Gnomad OTH exome

AF:

0.0295

GnomAD4 exome

AF:

0.0265

AC:

38725

AN:

1461720

Hom.:

624

Cov.:

AF XY:

0.0265

AC XY:

19252

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00445

Gnomad4 AMR exome

AF:

0.0202

Gnomad4 ASJ exome

AF:

0.0316

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0176

Gnomad4 FIN exome

AF:

0.00549

Gnomad4 NFE exome

AF:

0.0298

Gnomad4 OTH exome

AF:

0.0277

GnomAD4 genome

AF:

0.0189

AC:

2878

AN:

152250

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1309

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00518

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0203

Gnomad4 FIN

AF:

0.00387

Gnomad4 NFE

AF:

0.0286

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0182

Hom.:

Bravo

AF:

0.0197

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0312

EpiControl

AF:

0.0287

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 11

Uncertain:1Benign:3

Jun 22, 2017

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 10, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Mar 10, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hereditary spastic paraplegia

Benign:1

Jun 18, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.26

Position offset: -14

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