rs1060197

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015915.5(ATL1):c.351G>A(p.Glu117Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 1,613,442 control chromosomes in the GnomAD database, including 445,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 48597 hom., cov: 32)

Exomes 𝑓: 0.74 ( 397022 hom. )

Consequence

ATL1
NM_015915.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13O:1

Conservation

PhyloP100: 2.37

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 14-50591009-G-A is Benign according to our data. Variant chr14-50591009-G-A is described in ClinVar as [Benign]. Clinvar id is 21530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-50591009-G-A is described in Lovd as [Pathogenic]. Variant chr14-50591009-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATL1	NM_015915.5 link	c.351G>A	p.Glu117Glu	synonymous_variant	Exon 3 of 14	ENST00000358385.12	NP_056999.2	Q8WXF7-1A0A0S2Z5B0Q53F53
ATL1	NM_001127713.1 link	c.351G>A	p.Glu117Glu	synonymous_variant	Exon 4 of 14		NP_001121185.1	Q8WXF7-2A0A0S2Z5A2Q53F53
ATL1	NM_181598.4 link	c.351G>A	p.Glu117Glu	synonymous_variant	Exon 3 of 13		NP_853629.2	Q8WXF7-2A0A0S2Z5A2Q53F53
ATL1	XM_047431430.1 link	c.351G>A	p.Glu117Glu	synonymous_variant	Exon 4 of 15		XP_047287386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATL1	ENST00000358385.12 link	c.351G>A	p.Glu117Glu	synonymous_variant	Exon 3 of 14	1	NM_015915.5	ENSP00000351155.7		Q8WXF7-1

Frequencies

GnomAD3 genomes

AF:

0.793

AC:

120635

AN:

152050

Hom.:

48554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.931

Gnomad AMI

AF:

0.777

Gnomad AMR

AF:

0.795

Gnomad ASJ

AF:

0.764

Gnomad EAS

AF:

0.820

Gnomad SAS

AF:

0.755

Gnomad FIN

AF:

0.746

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.763

GnomAD3 exomes

AF:

0.764

AC:

191897

AN:

251018

Hom.:

73975

AF XY:

0.755

AC XY:

102466

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.932

Gnomad AMR exome

AF:

0.828

Gnomad ASJ exome

AF:

0.765

Gnomad EAS exome

AF:

0.828

Gnomad SAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.760

Gnomad NFE exome

AF:

0.719

Gnomad OTH exome

AF:

0.746

GnomAD4 exome

AF:

0.736

AC:

1074778

AN:

1461274

Hom.:

397022

Cov.:

AF XY:

0.734

AC XY:

533592

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.936

Gnomad4 AMR exome

AF:

0.824

Gnomad4 ASJ exome

AF:

0.763

Gnomad4 EAS exome

AF:

0.800

Gnomad4 SAS exome

AF:

0.739

Gnomad4 FIN exome

AF:

0.758

Gnomad4 NFE exome

AF:

0.721

Gnomad4 OTH exome

AF:

0.751

GnomAD4 genome

AF:

0.793

AC:

120737

AN:

152168

Hom.:

48597

Cov.:

AF XY:

0.794

AC XY:

59086

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.931

Gnomad4 AMR

AF:

0.795

Gnomad4 ASJ

AF:

0.764

Gnomad4 EAS

AF:

0.820

Gnomad4 SAS

AF:

0.753

Gnomad4 FIN

AF:

0.746

Gnomad4 NFE

AF:

0.720

Gnomad4 OTH

AF:

0.763

Alfa

AF:

0.753

Hom.:

31940

Bravo

AF:

0.804

Asia WGS

AF:

0.821

AC:

2856

AN:

3478

EpiCase

AF:

0.720

EpiControl

AF:

0.717

ClinVar

Significance: Benign

Submissions summary: Benign:13Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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. -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hereditary spastic paraplegia 3A

Benign:3Other:1

Feb 04, 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

- -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 18, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Neuropathy, hereditary sensory, type 1D

Benign:1

Jul 14, 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

- -

Hereditary spastic paraplegia 3A;C3150972:Neuropathy, hereditary sensory, type 1D

Benign:1

Aug 11, 2021

Fulgent Genetics, Fulgent Genetics

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

-0.47

CADD

Benign

7.8

DANN

Benign

0.60

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