rs35014209

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015915.5(ATL1):c.84A>G(p.Pro28Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,613,942 control chromosomes in the GnomAD database, including 17,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3045 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14390 hom. )

Consequence

ATL1
NM_015915.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11O:1

Conservation

PhyloP100: -2.70

Publications

13 publications found

Variant links:

Genes affected

ATL1 (HGNC:11231): (atlastin GTPase 1) The protein encoded by this gene is a GTPase and a Golgi body transmembrane protein. The encoded protein can form a homotetramer and has been shown to interact with spastin and with mitogen-activated protein kinase kinase kinase kinase 4. This protein may be involved in axonal maintenance as evidenced by the fact that defects in this gene are a cause of spastic paraplegia type 3. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ATL1 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 3A
Inheritance: AD, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
neuropathy, hereditary sensory, type 1D
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
hereditary sensory and autonomic neuropathy type 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ATL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 14-50587880-A-G is Benign according to our data. Variant chr14-50587880-A-G is described in ClinVar as Benign. ClinVar VariationId is 21534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATL1	NM_015915.5 link	c.84A>G	p.Pro28Pro	synonymous_variant	Exon 2 of 14	ENST00000358385.12	NP_056999.2	Q8WXF7-1A0A0S2Z5B0Q53F53
ATL1	NM_001127713.1 link	c.84A>G	p.Pro28Pro	synonymous_variant	Exon 3 of 14		NP_001121185.1	Q8WXF7-2A0A0S2Z5A2Q53F53
ATL1	NM_181598.4 link	c.84A>G	p.Pro28Pro	synonymous_variant	Exon 2 of 13		NP_853629.2	Q8WXF7-2A0A0S2Z5A2Q53F53
ATL1	XM_047431430.1 link	c.84A>G	p.Pro28Pro	synonymous_variant	Exon 3 of 15		XP_047287386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATL1	ENST00000358385.12 link	c.84A>G	p.Pro28Pro	synonymous_variant	Exon 2 of 14	1	NM_015915.5	ENSP00000351155.7		Q8WXF7-1

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27557

AN:

151988

Hom.:

3043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.0768

Gnomad SAS

AF:

0.0771

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.173

GnomAD2 exomes

AF:

0.131

AC:

32973

AN:

251472

AF XY:

0.126

show subpopulations

Gnomad AFR exome

AF:

0.319

Gnomad AMR exome

AF:

0.0894

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.0746

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.135

AC:

197220

AN:

1461836

Hom.:

14390

Cov.:

AF XY:

0.132

AC XY:

96205

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.326

AC:

10904

AN:

33480

American (AMR)

AF:

0.0931

AC:

4166

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

4817

AN:

26132

East Asian (EAS)

AF:

0.0740

AC:

2936

AN:

39698

South Asian (SAS)

AF:

0.0765

AC:

6603

AN:

86258

European-Finnish (FIN)

AF:

0.131

AC:

7012

AN:

53416

Middle Eastern (MID)

AF:

0.188

AC:

1082

AN:

5768

European-Non Finnish (NFE)

AF:

0.136

AC:

151137

AN:

1111964

Other (OTH)

AF:

0.142

AC:

8563

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

9916

19832

29747

39663

49579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5500

11000

16500

22000

27500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.181

AC:

27582

AN:

152106

Hom.:

3045

Cov.:

AF XY:

0.179

AC XY:

13287

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.316

AC:

13116

AN:

41466

American (AMR)

AF:

0.128

AC:

1961

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

654

AN:

3468

East Asian (EAS)

AF:

0.0770

AC:

398

AN:

5168

South Asian (SAS)

AF:

0.0779

AC:

376

AN:

4824

European-Finnish (FIN)

AF:

0.136

AC:

1434

AN:

10576

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9085

AN:

67992

Other (OTH)

AF:

0.170

AC:

360

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1079

2158

3237

4316

5395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.157

Hom.:

1125

Bravo

AF:

0.187

Asia WGS

AF:

0.0990

AC:

346

AN:

3478

EpiCase

AF:

0.137

EpiControl

AF:

0.137

ClinVar

Significance: Benign

Submissions summary: Benign:11Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Dec 30, 2013

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. -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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. -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 03, 2021

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary spastic paraplegia 3A

Benign:3Other:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Neuropathy, hereditary sensory, type 1D

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary spastic paraplegia

Benign:1

Dec 12, 2016

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.8

(source)

DANN

Benign

0.70

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over