dbSNP rs1060197: ATL1:p.Glu117Glu (chr14-50591009-G-A) – ACMG Classification: Benign (-21 pts)

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.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

Publications

22 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=-0.47).

BP6

Variant 14-50591009-G-A is Benign according to our data. Variant chr14-50591009-G-A is described in ClinVar as Benign. ClinVar VariationId is 21530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015915.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATL1	NM_015915.5	MANE Select	c.351G>A	p.Glu117Glu	synonymous	Exon 3 of 14	NP_056999.2
ATL1	NM_001127713.1		c.351G>A	p.Glu117Glu	synonymous	Exon 4 of 14	NP_001121185.1
ATL1	NM_181598.4		c.351G>A	p.Glu117Glu	synonymous	Exon 3 of 13	NP_853629.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATL1	ENST00000358385.12	TSL:1 MANE Select	c.351G>A	p.Glu117Glu	synonymous	Exon 3 of 14	ENSP00000351155.7
ATL1	ENST00000441560.6	TSL:1	c.351G>A	p.Glu117Glu	synonymous	Exon 4 of 14	ENSP00000413675.2
ATL1	ENST00000682037.1		c.351G>A	p.Glu117Glu	synonymous	Exon 3 of 14	ENSP00000508289.1

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

GnomAD2 exomes

AF:

0.764

AC:

191897

AN:

251018

AF XY:

0.755

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 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

African (AFR)

AF:

0.936

AC:

31320

AN:

33472

American (AMR)

AF:

0.824

AC:

36828

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.763

AC:

19932

AN:

26126

East Asian (EAS)

AF:

0.800

AC:

31708

AN:

39658

South Asian (SAS)

AF:

0.739

AC:

63754

AN:

86240

European-Finnish (FIN)

AF:

0.758

AC:

40427

AN:

53306

Middle Eastern (MID)

AF:

0.711

AC:

4098

AN:

5766

European-Non Finnish (NFE)

AF:

0.721

AC:

801370

AN:

1111614

Other (OTH)

AF:

0.751

AC:

45341

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

14812

29624

44436

59248

74060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20040

40080

60120

80160

100200

<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:

0.793

AC:

120737

AN:

152168

Hom.:

48597

Cov.:

AF XY:

0.794

AC XY:

59086

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.931

AC:

38685

AN:

41542

American (AMR)

AF:

0.795

AC:

12167

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.764

AC:

2651

AN:

3470

East Asian (EAS)

AF:

0.820

AC:

4244

AN:

5174

South Asian (SAS)

AF:

0.753

AC:

3624

AN:

4814

European-Finnish (FIN)

AF:

0.746

AC:

7890

AN:

10574

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.720

AC:

48949

AN:

67980

Other (OTH)

AF:

0.763

AC:

1611

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1220

2440

3659

4879

6099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.754

Hom.:

35583

Bravo

AF:

0.804

Asia WGS

AF:

0.821

AC:

2856

AN:

3478

EpiCase

AF:

0.720

EpiControl

AF:

0.717

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Hereditary spastic paraplegia 3A (4)

not provided (3)

Hereditary spastic paraplegia (1)

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

Neuropathy, hereditary sensory, type 1D (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

7.8

(source)

DANN

Benign

0.60

PhyloP100

2.4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over